Neoplasms, Breast
Conditions
Keywords
trastuzumab, ErbB2, paclitaxel, Herceptin, Taxol, ErbB1, metastatic breast cancer, Stage IV breast cancer, lapatinib
Brief summary
This study was originally designed as a Phase III randomized, double blind, placebo controlled study to assess the safety and tolerability, and efficacy of paclitaxel plus trastuzumab plus lapatinib compared with paclitaxel plus trastuzumab plus placebo in women with ErbB2 overexpressing metastatic breast cancer. The planned study was a two stage design with an initial open-label safety stage to be conducted in approximately 65 subjects followed by a randomized phase conducted in a further 700 subjects. The open-label part of the study sequentially enrolled three cohorts with patients receiving a different dose combination of paclitaxel, trastuzumab and lapatinib. Following poor recruitment rate in the open label stage, the randomized stage of the study was terminated, thus no subjects were enrolled into the randomization stage.
Detailed description
The primary objective of this study was to evaluate and compare time to progression (TTP). The Primary objective for open label phase was to determine the safety and tolerability of lapatinib when administered in combination with both paclitaxel and trastuzumab. The study first enrolled an open label safety cohort of 20 patients to assess the tolerability of the triplet combination. This was a 1 arm, 3 cohort study stage. Open-label Phase: Patients were sequentially enrolled into three cohorts and received an open-label combination of paclitaxel, trastuzumab and lapatinib: Cohort 1 received paclitaxel 80mg/m2 IV weekly for 3 weeks of a 4 week cycle, trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly, and lapatinib 1000 mg PO daily. Cohort 2 received paclitaxel 70mg/m2 IV weekly for 3 weeks of a 4 week cycle, trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly, and lapatinib 1000 mg PO daily. Cohort 3 paclitaxel 80mg/m2 IV weekly for 3 weeks of a 4 week cycle, trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly, and lapatinib 750 mg PO daily. Randomized Phase: was terminated following the poor recruitment rate in the open-label safety stage. No subjects were enrolled into the randomization stage. In summary, at approximately 3.5 years the primary analysis which included demographics, efficacy and safety were conducted; at approximately 7 years protocol amendment 7 cancelled collection of efficacy endpoints, and only key safety endpoints were to be collected; the final analysis was performed at approximately 14 years.
Interventions
DRUGlapatinib
(GW572016) 1000 mg QD
DRUGpaclitaxel
80 mg/m2 IV weekly for three weeks
DRUGtrastuzumab
4 mg/kg loading dose and 2 mg/kg weekly IV
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed invasive breast cancer with stage IV disease * If trastuzumab was administered in the adjuvant setting, \>12 months must have elapsed since discontinuation of trastuzumab therapy * If a taxane was administered in the neoadjuvant or adjuvant setting, progression must have occurred ≥12 months after completion of this treatment * Had tumors that overexpress ErbB2 defined as either: 3+ by IHC OR c-erbB2 gene amplification by FISH OR 0, 1+, 2+ by IHC and c-erbB2 gene amplification by FISH. * Patients must have tumor tissue available for central testing, and must have Measurable lesion(s) according to RECIST * Subjects must be females of at least 18 years Non-childbearing potential or Childbearing potential but using adequate contraception * Radiotherapy to a limited area other than the sole site of measurable and assessable disease is allowed; however, patients must have completed treatment and recovered from all acute treatment-related toxicities prior to administration of the first dose of study medication * Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of randomized therapy. Prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1 * For those patients whose disease is estrogen receptor positive+ and/or progesterone receptor + one the following criteria should be met: Patients with visceral disease that requires chemotherapy (eg., patients with liver or lung metastases) or Rapidly progressing/life threatening disease, as determined by the investigator or Patients who received hormonal therapy and are no longer benefiting from this therapy; * Able to swallow and retain oral medication * Cardiac ejection fraction within institutional range of normal * Patient must have adequate organ function
Exclusion criteria
* Pregnant or lactating females; * Received prior chemotherapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for metastatic disease, prior hormonal therapy is permitted but must be discontinued a minimum of 7 days prior to randomization; * Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Patients with ulcerative colitis are also excluded; * History of other malignancy; however, patients who have been disease-free for five years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible; * Concurrent disease or condition that would make the patient inappropriate for study participation, or any serious medical disorder that would interfere with the patient's safety; * Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment; * Peripheral neuropathy of Grade 2 or greater; * Active or uncontrolled infection; * Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent; * Known history of uncontrolled or symptomatic angina, arrhythmias, conduction abnormalities or congestive heart failure; * Known history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis; * Concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy); * Concurrent treatment with an investigational agent or participation in another clinical trial; * Concurrent treatment with any medication on the prohibited medications list. * Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of treatment. Hormonal therapy needs to be discontinued at least 7 days before the first dose of treatment. * Prior therapy with an ErbB2 inhibitor, other than trastuzumab in the adjuvant setting; * A known immediate or delayed hypersensitivity reaction to drugs chemically related to lapatinib or excipients; * A known immediate or delayed hypersensitivity reaction to drugs chemically related to paclitaxel or excipients; * A known immediate or delayed hypersensitivity reaction to drugs chemically related to trastuzumab or excipients; * Non compliance with any of the screening procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response (OR): Percentage of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator | From the date of the first dose of investigational product to end of study, up to approx. 7 years | OR is defined as the number of participants achieving either a CR or PR, per Response Evaluation Criteria in Solid Tumors (RECIST). The best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made \>=28 days after the original response. Participants with an unknown or missing response are treated as non-responders. |
| Change From Baseline in Body Temperature at the Indicated Time Points | Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years | Body temperature was measured at Baseline and every 4 weeks thereafter up to withdrawal/study completion and at the 30 day follow-up visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Number of Participants With at Least 1 Event of Left Ventricular Ejection Fraction Decrease With the Indicated Characteristics | Baseline and every 8 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years | Events of left ventricular ejection fraction (LVEF) decrease were based on the number of participants who had an actual event and was characterized as serious, related to investigational product, leading to withdrawal from the study and/or fatal. |
| Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years | The Eastern Cooperative Oncology Group (ECOG) performance status scales and grades/criteria are used to assess how a participant's disease is progressing, to assess how the disease affects the daily living abilities of the participant, and to determine appropriate treatment and prognosis. Grade 0, fully active, able to carry on all pre-disease performance without restriction. Grade 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. Grade 2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about more than 50% of waking hours. Grade 3, capable of only limited selfcare; confined to bed or chair more than 50% of waking hours. Grade 4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. Grade 5, dead. |
| Number of Participants Who Received Any Concomitant Medications During the Study Period | withdrawal/study completion, up to approx. 3.5 years | Number of participants who received any concomitant medication along with study drugs (lapatinib, trastuzumab and paclitaxel) were counted during the treatment period. |
| Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Mean/Standard Deviation | From the date of the first dose of the investigational product to end of study, up to approx. 14 years | Extent of exposure is defined as the duration of the treatment administered during the study. The mean duration of exposure to lapatinib, trastuzumab and paclitaxel is calculated as the number of weeks between the start and end of treatment. |
| Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Median/Min-Max | From the date of the first dose of the investigational product to end of study, up to approx. 14 years | Extent of exposure is defined as the duration of the treatment administered during the study. The mean duration of exposure to lapatinib, trastuzumab and paclitaxel is calculated as the number of weeks between the start and end of treatment. |
| Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | From the date of the first dose of investigational product until 30 days after the last dose of investigational product, up to approx. 14 years | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations. Refer to the general AE/SAE module for a list of non-serious AEs and SAEs. |
| Number of Participants Who Died Due to Any Cause | From the date of the first dose of investigational product until last patient last visit, up to approximately 14 years | Number of participants who died due to any cause throughout the study including off-treatment deaths (on-treatment deaths are reported for the All-Cause Mortality in the AE section). |
| Number of Events of Diarrhea With the Indicated Characteristics | From the date of the first dose of investigational product until 30 days after the last dose of investigational product, up to approx. 3.5 years | Events of diarrhea are characterized as serious, related to investigational product, leading to withdrawal from the study and fatal. Participants could have been counted in more than one category. |
| Number of Events of Rash With the Indicated Characteristics | From the date of the first dose of investigational product until 30 days after the last dose of investigational product, up to approx. 3.5 years | Events of rash are characterized as serious, related to investigational product, leading to withdrawal from the study and fatal. Participants could have been counted in more than one category. |
| Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years | Blood samples for clinical laboratory evaluation were taken at Baseline prior to the administration of investigational product and thereafter at each scheduled visit. Haematology parameters included haemoglobin, total white blood cell count (WBC), neutrophils, lymphocytes and platelets. Hematology data was summarized by the National Cancer Institute's Common toxicity criteria for adverse events (NCI CTCAE) toxicity grade (Version 3.0). Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling; Grade 5, death. |
| Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years | Blood samples for clinical laboratory evaluation were taken at Baseline prior to the administration of investigational product and thereafter at each scheduled visit. Clinical chemistry parameters included values \> upper limit of normal (ULN)=Hyper; values \< lower limit of normal (LLN)=Hypo of sodium (Hypernatraemia and Hyponatraemia), potassium (Hyperkalaemia and Hypokalaemia), calcium (Hypercalcaemia and Hypocalcaemia), glucose (Hyperglycaemia and Hyperglycaemia), creatinine (if \>2 milligram per deciliter \[mg/dL\]), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phophatase, total bilirubin (if available bilirubin fractionation is recommended if the total bilirubin is \> twice of ULN), and albumin. Clinical chemistry data was summarized by National Cancer Institute's Common toxicity criteria for adverse events (NCI CTCAE) toxicity grade (Version 3.0). Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling; Grade 5, death. |
| Number of Events of Hepatotoxicity With the Indicated Characteristics | From the date of the first dose of investigational product until 30 days after the last dose of investigational product, up to approx. 3.5 years | Events of hepatotoxicity are characterized as serious, related to investigational product, leading to withdrawal from the study and fatal. Participants could have been counted in more than one category. |
| Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years | Blood pressure measurement included systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Baseline and every 4 weeks thereafter up to withdrawal/study completion and at the 30 day follow-up visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in Heart Rate at the Indicated Time Points | Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years | Heart rate was measured at Baseline and every 4 weeks thereafter up to withdrawal/study completion and at the 30 day follow-up visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR), as Assessed by the Investigator | From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer, up to approx. 7 years | DoR is defined for the subset of participants who had a confirmed CR (disappearance of all TLs and non-TLs) or PR (\>=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL\[s\]) as the time from the first documented evidence of a CR or PR until the first documentation of radiological PD or death due to breast cancer, if sooner. PD is defined as \>=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. For participants who did not progress or die, DoR was censored on the date of the last radiological scan. If a participant had only a Baseline visit or did not have a date of a radiological scan that was later than the date of initiation of anti-cancer therapy, DoR was censored at the start date of treatment. |
| Percentage of Participants With Clinical Benefit (Complete Response (CR), Partial Response (PR), and Stable Disease [SD] for at Least 24 Weeks) as Assessed by Investigator | From the date of the first dose of investigational product until the first documented evidence of a PR or CR or SD until the earlier of the date of disease progression or the date of death due to breast cancer, up to approx. 7 years | Clinical benefit is defined as the percentage of participants achieving either a CR or PR or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of the LD of target lesions, taking as a reference, the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions), taking as reference, the smallest sum LD since the treatment started) for at least 24 weeks. This was based on confirmed responses from the investigator assessment of clinical benefit. |
| Progression-free Survival as Assessed by the Investigator | From the date of the first dose of investigational product until the earlier of the date of disease progression or death due to any cause, up to approx. 7 years | Progression-free survival is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. Disease progression was based on the investigator's assessments of the objective evidence (e.g., radiological scans and medical photographs). For participants who do not progress, or die, progression-free survival was censored at the time of the last investigator assessed radiological scan preceding the initiation of any alternative anti-cancer therapy. Progression-free survival was summarized using Kaplan-Meier curves. |
| Time to Response as Assessed by the Investigator | From the date of the first dose of investigational product until the first documented evidence of a PR or CR, up to approx. 7 years | Time to Response was defined for subjects who had a confirmed CR or PR as the time from first dose until first documented evidence of partial or complete tumour response (whichever status was recorded first). CR is defined as the disappearance of all TLs & non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s). PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. |
Countries
Belgium, United States
Participant flow
Recruitment details
Female participants (par.) with histologically confirmed invasive breast cancer (Stage IV disease) whose tumors overexpressed the ErbB2 protein, documented by either Immunohistochemistry (IHC) or fluorescence in situ hybridisation (FISH), were eligible for inclusion in this study.
Pre-assignment details
Participants who met inclusion criteria were sequentially enrolled into three cohorts and received the open-label triple combination of paclitaxel, trastuzumab and lapatinib. The planned randomized phase of the study was terminated following the poor recruitment rate in the Open-label Phase.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg Participants received an intravenous (IV) infusion of paclitaxel 80 milligrams per meter squared (mg/m\^2) over 60 minutes weekly for 3 weeks of a 4-week cycle plus an IV infusion of trastuzumab 4 mg per kilogram (mg/kg) loading dose and 2 mg/kg weekly plus a daily dose of 4 tablets of lapatinib (total daily dose 1000 mg) at approximately the same time every day, either 1 hour (or more) before a meal or 1 hour (or more) after a meal. | 29 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg Participants received an IV infusion of paclitaxel 70 mg/m\^2 over 60 minutes weekly for 3 weeks of a 4-week cycle plus an IV infusion of trastuzumab 4 mg/kg loading dose and 2 mg/kg weekly plus a daily dose of 4 tablets of lapatinib (total daily dose 1000 mg) at approximately the same time every day, either 1 hour (or more) before a meal or 1 hour (or more) after a meal. The paclitaxel dose was systematically increased to 80 mg/m\^2 after 2 cycles if 70 mg/m\^2 was tolerated. | 14 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg Participants received an IV infusion of paclitaxel 80 mg/m\^2 over 60 minutes weekly for 3 weeks of a 4-week cycle plus an IV infusion of trastuzumab 4 mg/kg loading dose and 2 mg/kg weekly plus a daily dose of 3 tablets of lapatinib (total daily dose 750 mg) at approximately the same time every day, either 1 hour (or more) before a meal or 1 hour (or more) after a meal. The lapatinib dose was systematically increased to 1000 mg after 2 cycles if the 750 mg dose was tolerated. | 20 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Disease progression | 1 | 1 | 2 |
| Overall Study | Lost to Follow-up | 3 | 1 | 1 |
| Overall Study | Non-compliant- study visits, trtmnts, req. surgery | 2 | 1 | 4 |
| Overall Study | Sponsor Terminated study | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 51.5 Years STANDARD_DEVIATION 11.08 | 56.1 Years STANDARD_DEVIATION 11.92 | 52.2 Years STANDARD_DEVIATION 13 | 52.7 Years STANDARD_DEVIATION 11.84 |
| Race/Ethnicity, Customized African American/African Heritage | 7 Participants | 2 Participants | 4 Participants | 13 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 22 Participants | 11 Participants | 16 Participants | 49 Participants |
| Sex: Female, Male Female | 29 Participants | 14 Participants | 20 Participants | 63 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 14 | 0 / 20 |
| other Total, other adverse events | 29 / 29 | 13 / 14 | 20 / 20 |
| serious Total, serious adverse events | 14 / 29 | 6 / 14 | 5 / 20 |
Outcome results
Primary
Change From Baseline in Body Temperature at the Indicated Time Points
Body temperature was measured at Baseline and every 4 weeks thereafter up to withdrawal/study completion and at the 30 day follow-up visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years
Population: Safety Population: all participants who were randomized and received at least one dose of investigational product.~Only those participants available at the specified time points were analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 100 | -0.100 Degree Celsius | Standard Deviation 0.9083 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 24 | 0.157 Degree Celsius | Standard Deviation 0.5006 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 28 | -0.094 Degree Celsius | Standard Deviation 0.4956 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 32 | -0.156 Degree Celsius | Standard Deviation 0.6077 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 36 | -0.215 Degree Celsius | Standard Deviation 0.5728 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 40 | 0.045 Degree Celsius | Standard Deviation 0.4634 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 44 | -0.182 Degree Celsius | Standard Deviation 0.4729 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 48 | -0.109 Degree Celsius | Standard Deviation 0.4571 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 52 | -0.222 Degree Celsius | Standard Deviation 1.0616 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 56 | 0.111 Degree Celsius | Standard Deviation 0.6489 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 60 | -0.070 Degree Celsius | Standard Deviation 0.5889 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 64 | -0.080 Degree Celsius | Standard Deviation 0.4662 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 68 | 0.286 Degree Celsius | Standard Deviation 0.6744 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 72 | 0.057 Degree Celsius | Standard Deviation 0.739 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 76 | 0.017 Degree Celsius | Standard Deviation 0.4834 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 80 | -0.150 Degree Celsius | Standard Deviation 0.6442 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 84 | 0.067 Degree Celsius | Standard Deviation 0.561 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 88 | -0.267 Degree Celsius | Standard Deviation 0.4131 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 92 | -0.200 Degree Celsius | Standard Deviation 0.8155 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 96 | -0.125 Degree Celsius | Standard Deviation 0.4573 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 4 | -0.229 Degree Celsius | Standard Deviation 0.5062 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 104 | -0.160 Degree Celsius | Standard Deviation 0.7436 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 108 | 0.080 Degree Celsius | Standard Deviation 0.6099 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 112 | 0.050 Degree Celsius | Standard Deviation 0.5 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 116 | 0.250 Degree Celsius | Standard Deviation 0.6403 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 120 | 0.200 Degree Celsius | Standard Deviation 0.4359 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 124 | 0.167 Degree Celsius | Standard Deviation 0.8083 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 128 | 0.200 Degree Celsius | Standard Deviation 1.4142 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 132 | -0.150 Degree Celsius | Standard Deviation 1.2021 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 136 | 0.000 Degree Celsius | Standard Deviation 1.2728 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 140 | 0.450 Degree Celsius | Standard Deviation 1.3435 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 144 | 1.300 Degree Celsius | — |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 148 | 0.700 Degree Celsius | — |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Withdrawal/Study Conclusion | -0.083 Degree Celsius | Standard Deviation 0.6833 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | 30 Day Follow-up | -0.092 Degree Celsius | Standard Deviation 0.6238 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 8 | 0.011 Degree Celsius | Standard Deviation 0.525 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 12 | 0.021 Degree Celsius | Standard Deviation 0.4374 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 16 | -0.052 Degree Celsius | Standard Deviation 0.5814 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 20 | 0.018 Degree Celsius | Standard Deviation 0.5712 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 48 | -0.200 Degree Celsius | Standard Deviation 0.1414 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 72 | -0.400 Degree Celsius | — |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 20 | -0.238 Degree Celsius | Standard Deviation 0.4138 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 56 | -0.240 Degree Celsius | Standard Deviation 0.6427 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 24 | -0.100 Degree Celsius | Standard Deviation 0.4138 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Withdrawal/Study Conclusion | -0.020 Degree Celsius | Standard Deviation 0.4367 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 28 | -0.529 Degree Celsius | Standard Deviation 0.4751 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 60 | -0.225 Degree Celsius | Standard Deviation 0.2754 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 32 | -0.237 Degree Celsius | Standard Deviation 0.2134 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 36 | -0.129 Degree Celsius | Standard Deviation 0.3946 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 64 | -0.150 Degree Celsius | Standard Deviation 0.1732 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 40 | -0.314 Degree Celsius | Standard Deviation 0.1952 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 44 | -0.217 Degree Celsius | Standard Deviation 0.392 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 68 | -0.550 Degree Celsius | Standard Deviation 0.0707 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 4 | -0.242 Degree Celsius | Standard Deviation 0.3605 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 8 | -0.154 Degree Celsius | Standard Deviation 0.4294 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | 30 Day Follow-up | -0.400 Degree Celsius | Standard Deviation 0.5074 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 12 | -0.567 Degree Celsius | Standard Deviation 0.496 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 52 | -0.340 Degree Celsius | Standard Deviation 0.3286 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 16 | -0.127 Degree Celsius | Standard Deviation 0.488 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 4 | 0.078 Degree Celsius | Standard Deviation 0.5976 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 48 | 0.300 Degree Celsius | — |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Withdrawal/Study Conclusion | 0.237 Degree Celsius | Standard Deviation 0.5999 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 8 | 0.247 Degree Celsius | Standard Deviation 0.4652 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 24 | 0.017 Degree Celsius | Standard Deviation 0.5193 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 40 | 0.450 Degree Celsius | Standard Deviation 0.9192 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 12 | 0.173 Degree Celsius | Standard Deviation 0.4636 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 36 | 0.533 Degree Celsius | Standard Deviation 0.3786 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 28 | 0.300 Degree Celsius | Standard Deviation 0.3536 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 16 | 0.121 Degree Celsius | Standard Deviation 0.5494 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | 30 Day Follow-up | 0.140 Degree Celsius | Standard Deviation 0.532 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 44 | 0.250 Degree Celsius | Standard Deviation 0.0707 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 20 | 0.300 Degree Celsius | Standard Deviation 0.3536 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Body Temperature at the Indicated Time Points | Week 32 | 0.000 Degree Celsius | Standard Deviation 0.2 |
Primary
Change From Baseline in Heart Rate at the Indicated Time Points
Heart rate was measured at Baseline and every 4 weeks thereafter up to withdrawal/study completion and at the 30 day follow-up visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years
Population: Safety Population. Safety Population: all participants who were randomized and received at least one dose of investigational product.~Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 108 | -8.750 Beats per minute (BPM) | Standard Deviation 6.4485 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 4 | -1.714 Beats per minute (BPM) | Standard Deviation 10.9099 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 28 | -4.313 Beats per minute (BPM) | Standard Deviation 16.0155 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 32 | -4.933 Beats per minute (BPM) | Standard Deviation 16.6496 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 36 | -5.000 Beats per minute (BPM) | Standard Deviation 13.0128 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 40 | -1.000 Beats per minute (BPM) | Standard Deviation 14.1614 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 44 | -3.000 Beats per minute (BPM) | Standard Deviation 11.1624 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 48 | -5.500 Beats per minute (BPM) | Standard Deviation 8.1955 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 52 | -1.889 Beats per minute (BPM) | Standard Deviation 14.4866 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 56 | -2.000 Beats per minute (BPM) | Standard Deviation 13.4907 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 60 | -2.600 Beats per minute (BPM) | Standard Deviation 13.3766 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 64 | -4.667 Beats per minute (BPM) | Standard Deviation 16.1245 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 68 | -8.286 Beats per minute (BPM) | Standard Deviation 21.1638 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 72 | -0.714 Beats per minute (BPM) | Standard Deviation 21.0295 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 76 | -0.500 Beats per minute (BPM) | Standard Deviation 16.6463 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 80 | 0.800 Beats per minute (BPM) | Standard Deviation 14.481 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 84 | 9.200 Beats per minute (BPM) | Standard Deviation 21.1234 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 88 | 2.200 Beats per minute (BPM) | Standard Deviation 24.611 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 92 | -2.400 Beats per minute (BPM) | Standard Deviation 10.139 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 96 | -8.250 Beats per minute (BPM) | Standard Deviation 7.6322 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 100 | -6.750 Beats per minute (BPM) | Standard Deviation 13.1751 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 104 | -6.800 Beats per minute (BPM) | Standard Deviation 15.3525 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 112 | -0.667 Beats per minute (BPM) | Standard Deviation 15.0444 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 116 | -4.667 Beats per minute (BPM) | Standard Deviation 14.5717 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 120 | -7.667 Beats per minute (BPM) | Standard Deviation 9.4516 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 124 | -5.333 Beats per minute (BPM) | Standard Deviation 13.2035 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 128 | 1.000 Beats per minute (BPM) | Standard Deviation 21.2132 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 132 | -4.000 Beats per minute (BPM) | Standard Deviation 14.1421 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 136 | -4.000 Beats per minute (BPM) | Standard Deviation 15.5563 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 140 | -3.500 Beats per minute (BPM) | Standard Deviation 16.2635 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 144 | 3.000 Beats per minute (BPM) | — |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 148 | 6.000 Beats per minute (BPM) | — |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Withdrawal/Study Conclusion | -1.435 Beats per minute (BPM) | Standard Deviation 19.3481 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | 30 Day Follow-up | 0.560 Beats per minute (BPM) | Standard Deviation 13.1564 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 8 | -5.667 Beats per minute (BPM) | Standard Deviation 14.7908 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 12 | -0.217 Beats per minute (BPM) | Standard Deviation 10.7109 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 16 | -0.478 Beats per minute (BPM) | Standard Deviation 13.4667 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 24 | -0.476 Beats per minute (BPM) | Standard Deviation 16.7768 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 4 | -3.417 Beats per minute (BPM) | Standard Deviation 26.3593 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | 30 Day Follow-up | -7.889 Beats per minute (BPM) | Standard Deviation 17.3526 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 24 | -5.300 Beats per minute (BPM) | Standard Deviation 15.1808 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 60 | 1.500 Beats per minute (BPM) | Standard Deviation 15.0222 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 28 | -1.429 Beats per minute (BPM) | Standard Deviation 17.7281 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Withdrawal/Study Conclusion | -7.900 Beats per minute (BPM) | Standard Deviation 19.399 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 32 | -0.500 Beats per minute (BPM) | Standard Deviation 11.1098 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 64 | 0.000 Beats per minute (BPM) | Standard Deviation 15.384 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 36 | 4.857 Beats per minute (BPM) | Standard Deviation 18.4791 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 40 | -3.571 Beats per minute (BPM) | Standard Deviation 17.6149 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 68 | 1.000 Beats per minute (BPM) | Standard Deviation 25.4558 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 44 | -5.000 Beats per minute (BPM) | Standard Deviation 17.9778 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 48 | -2.500 Beats per minute (BPM) | Standard Deviation 12.9422 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 72 | 19.000 Beats per minute (BPM) | — |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 52 | -2.000 Beats per minute (BPM) | Standard Deviation 11.8533 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 8 | -3.231 Beats per minute (BPM) | Standard Deviation 16.8481 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 12 | -0.417 Beats per minute (BPM) | Standard Deviation 15.6812 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 56 | -2.000 Beats per minute (BPM) | Standard Deviation 15.2151 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 16 | 2.625 Beats per minute (BPM) | Standard Deviation 15.1369 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 4 | 3.333 Beats per minute (BPM) | Standard Deviation 12.1268 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 44 | -0.500 Beats per minute (BPM) | Standard Deviation 10.6066 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 36 | 7.000 Beats per minute (BPM) | Standard Deviation 11.5326 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 8 | 5.353 Beats per minute (BPM) | Standard Deviation 10.7642 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Heart Rate at the Indicated Time Points | 30 Day Follow-up | 13.200 Beats per minute (BPM) | Standard Deviation 11.606 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 28 | 3.600 Beats per minute (BPM) | Standard Deviation 8.5615 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 12 | -2.875 Beats per minute (BPM) | Standard Deviation 10.6074 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 48 | -14.000 Beats per minute (BPM) | — |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Withdrawal/Study Conclusion | 7.750 Beats per minute (BPM) | Standard Deviation 9.8814 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 16 | -1.917 Beats per minute (BPM) | Standard Deviation 10.9084 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 32 | 0.333 Beats per minute (BPM) | Standard Deviation 10.5987 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 40 | -2.500 Beats per minute (BPM) | Standard Deviation 9.1924 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Heart Rate at the Indicated Time Points | Week 24 | 5.167 Beats per minute (BPM) | Standard Deviation 10.2843 |
Primary
Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points
Blood pressure measurement included systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Baseline and every 4 weeks thereafter up to withdrawal/study completion and at the 30 day follow-up visit. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years
Population: Safety Population: all participants who were randomized and received at least one dose of investigational product.~Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 24 | -1.2 Millimeter of mercury (mmHg) | Standard Deviation 11.3 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 92 | 10.4 Millimeter of mercury (mmHg) | Standard Deviation 16.59 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 96 | -0.5 Millimeter of mercury (mmHg) | Standard Deviation 4.12 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 100 | 10.8 Millimeter of mercury (mmHg) | Standard Deviation 7.53 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 104 | 7.0 Millimeter of mercury (mmHg) | Standard Deviation 16 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 108 | 4.6 Millimeter of mercury (mmHg) | Standard Deviation 7.89 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 112 | 12.3 Millimeter of mercury (mmHg) | Standard Deviation 10.72 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 116 | 9.3 Millimeter of mercury (mmHg) | Standard Deviation 15.22 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 120 | 13.3 Millimeter of mercury (mmHg) | Standard Deviation 19.86 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 124 | 7.3 Millimeter of mercury (mmHg) | Standard Deviation 8.5 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 128 | -11.0 Millimeter of mercury (mmHg) | Standard Deviation 9.9 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 132 | -10.5 Millimeter of mercury (mmHg) | Standard Deviation 10.61 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 136 | -4.0 Millimeter of mercury (mmHg) | Standard Deviation 18.38 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 140 | 4.5 Millimeter of mercury (mmHg) | Standard Deviation 23.33 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 144 | 10.0 Millimeter of mercury (mmHg) | Standard Deviation 0 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 148 | 25.0 Millimeter of mercury (mmHg) | — |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Withdrawal/Study Conclusion | 0.5 Millimeter of mercury (mmHg) | Standard Deviation 16.13 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, 30 Day Follow-up | 2.4 Millimeter of mercury (mmHg) | Standard Deviation 19.18 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 4 | -2.5 Millimeter of mercury (mmHg) | Standard Deviation 10.36 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 24 | 2.9 Millimeter of mercury (mmHg) | Standard Deviation 13.87 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 8 | -0.6 Millimeter of mercury (mmHg) | Standard Deviation 11.41 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 12 | -0.3 Millimeter of mercury (mmHg) | Standard Deviation 10.19 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 12 | 3.2 Millimeter of mercury (mmHg) | Standard Deviation 18.46 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 16 | -3.4 Millimeter of mercury (mmHg) | Standard Deviation 12.98 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 28 | 2.3 Millimeter of mercury (mmHg) | Standard Deviation 19.1 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 20 | -3.0 Millimeter of mercury (mmHg) | Standard Deviation 12.65 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 68 | -11.0 Millimeter of mercury (mmHg) | Standard Deviation 6.4 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 28 | -1.8 Millimeter of mercury (mmHg) | Standard Deviation 14.27 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 32 | 3.2 Millimeter of mercury (mmHg) | Standard Deviation 23.11 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 32 | -2.2 Millimeter of mercury (mmHg) | Standard Deviation 13.7 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 36 | -7.2 Millimeter of mercury (mmHg) | Standard Deviation 6.48 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 8 | 4.6 Millimeter of mercury (mmHg) | Standard Deviation 12.35 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 40 | -9.3 Millimeter of mercury (mmHg) | Standard Deviation 11.36 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 36 | 1.6 Millimeter of mercury (mmHg) | Standard Deviation 15.85 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 44 | -9.0 Millimeter of mercury (mmHg) | Standard Deviation 6.59 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 48 | -3.9 Millimeter of mercury (mmHg) | Standard Deviation 7.57 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 16 | 0.8 Millimeter of mercury (mmHg) | Standard Deviation 18.1 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 52 | -7.4 Millimeter of mercury (mmHg) | Standard Deviation 13.46 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 56 | -5.1 Millimeter of mercury (mmHg) | Standard Deviation 8.62 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 60 | -3.6 Millimeter of mercury (mmHg) | Standard Deviation 11.56 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 64 | -7.7 Millimeter of mercury (mmHg) | Standard Deviation 12.27 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 72 | 3.0 Millimeter of mercury (mmHg) | Standard Deviation 9.26 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 76 | -4.8 Millimeter of mercury (mmHg) | Standard Deviation 5 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 80 | -3.5 Millimeter of mercury (mmHg) | Standard Deviation 5.58 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 84 | -5.8 Millimeter of mercury (mmHg) | Standard Deviation 9.5 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 88 | -9.3 Millimeter of mercury (mmHg) | Standard Deviation 11.48 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 92 | -3.8 Millimeter of mercury (mmHg) | Standard Deviation 5.26 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 96 | -7.3 Millimeter of mercury (mmHg) | Standard Deviation 6.29 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 100 | -4.4 Millimeter of mercury (mmHg) | Standard Deviation 6.5 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 104 | -4.6 Millimeter of mercury (mmHg) | Standard Deviation 9.1 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 108 | -2.0 Millimeter of mercury (mmHg) | Standard Deviation 5.89 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 116 | -8.5 Millimeter of mercury (mmHg) | Standard Deviation 9.33 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 120 | -6.0 Millimeter of mercury (mmHg) | Standard Deviation 7.94 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 124 | -6.0 Millimeter of mercury (mmHg) | Standard Deviation 6 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 128 | -12.5 Millimeter of mercury (mmHg) | Standard Deviation 0.71 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 132 | -14.5 Millimeter of mercury (mmHg) | Standard Deviation 4.95 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 136 | -17.0 Millimeter of mercury (mmHg) | Standard Deviation 4.24 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 140 | -7.5 Millimeter of mercury (mmHg) | Standard Deviation 10.61 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 144 | 0.0 Millimeter of mercury (mmHg) | Standard Deviation 0 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 148 | 1.0 Millimeter of mercury (mmHg) | — |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Withdrawal/Study Conclusion | -0.5 Millimeter of mercury (mmHg) | Standard Deviation 11.39 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 40 | -2.2 Millimeter of mercury (mmHg) | Standard Deviation 24.44 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, 30 Day Follow-up | -0.8 Millimeter of mercury (mmHg) | Standard Deviation 11.96 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 4 | 0.5 Millimeter of mercury (mmHg) | Standard Deviation 16.29 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 44 | 2.7 Millimeter of mercury (mmHg) | Standard Deviation 14.47 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 48 | 6.5 Millimeter of mercury (mmHg) | Standard Deviation 18.76 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 20 | 1.7 Millimeter of mercury (mmHg) | Standard Deviation 17.8 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 52 | 7.7 Millimeter of mercury (mmHg) | Standard Deviation 14.47 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 56 | 8.4 Millimeter of mercury (mmHg) | Standard Deviation 13.53 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 60 | 9.3 Millimeter of mercury (mmHg) | Standard Deviation 22.07 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 64 | 3.5 Millimeter of mercury (mmHg) | Standard Deviation 16.53 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 68 | 0.1 Millimeter of mercury (mmHg) | Standard Deviation 10.71 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 72 | 7.1 Millimeter of mercury (mmHg) | Standard Deviation 13.25 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 76 | 4.5 Millimeter of mercury (mmHg) | Standard Deviation 12.96 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 80 | 8.7 Millimeter of mercury (mmHg) | Standard Deviation 6.92 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 84 | 7.0 Millimeter of mercury (mmHg) | Standard Deviation 20.2 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 88 | -2.7 Millimeter of mercury (mmHg) | Standard Deviation 16.32 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 68 | -3.5 Millimeter of mercury (mmHg) | Standard Deviation 7.78 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 60 | -17.0 Millimeter of mercury (mmHg) | Standard Deviation 9.31 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 72 | -16.0 Millimeter of mercury (mmHg) | — |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 44 | -2.3 Millimeter of mercury (mmHg) | Standard Deviation 10.33 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 64 | -11.3 Millimeter of mercury (mmHg) | Standard Deviation 11.24 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, 30 Day Follow-up | -3.9 Millimeter of mercury (mmHg) | Standard Deviation 17.03 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 68 | -6.5 Millimeter of mercury (mmHg) | Standard Deviation 12.02 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 4 | -7.2 Millimeter of mercury (mmHg) | Standard Deviation 20.7 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 72 | -20.0 Millimeter of mercury (mmHg) | — |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 36 | -8.7 Millimeter of mercury (mmHg) | Standard Deviation 12.19 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 4 | -3.9 Millimeter of mercury (mmHg) | Standard Deviation 10.5 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 32 | -6.3 Millimeter of mercury (mmHg) | Standard Deviation 10.24 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 32 | -16.4 Millimeter of mercury (mmHg) | Standard Deviation 10.03 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 8 | -8.9 Millimeter of mercury (mmHg) | Standard Deviation 11.54 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 24 | -1.8 Millimeter of mercury (mmHg) | Standard Deviation 11.81 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 60 | -6.3 Millimeter of mercury (mmHg) | Standard Deviation 6.24 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 12 | -6.2 Millimeter of mercury (mmHg) | Standard Deviation 10.37 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 36 | -3.3 Millimeter of mercury (mmHg) | Standard Deviation 6.4 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 48 | -0.2 Millimeter of mercury (mmHg) | Standard Deviation 8.13 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 16 | -3.2 Millimeter of mercury (mmHg) | Standard Deviation 8.42 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 56 | -3.4 Millimeter of mercury (mmHg) | Standard Deviation 7.99 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 40 | -0.7 Millimeter of mercury (mmHg) | Standard Deviation 13.76 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Withdrawal/Study Conclusion | -0.4 Millimeter of mercury (mmHg) | Standard Deviation 12.08 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 20 | -1.6 Millimeter of mercury (mmHg) | Standard Deviation 9.53 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 28 | -5.7 Millimeter of mercury (mmHg) | Standard Deviation 20.38 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, 30 Day Follow-up | 0.8 Millimeter of mercury (mmHg) | Standard Deviation 11.62 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 64 | -5.3 Millimeter of mercury (mmHg) | Standard Deviation 8.54 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 40 | -3.4 Millimeter of mercury (mmHg) | Standard Deviation 9.62 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 16 | -6.6 Millimeter of mercury (mmHg) | Standard Deviation 15.26 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 24 | -1.8 Millimeter of mercury (mmHg) | Standard Deviation 6.56 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 44 | -3.8 Millimeter of mercury (mmHg) | Standard Deviation 9.83 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 8 | -8.6 Millimeter of mercury (mmHg) | Standard Deviation 22.25 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 12 | -6.9 Millimeter of mercury (mmHg) | Standard Deviation 17.09 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 48 | -6.7 Millimeter of mercury (mmHg) | Standard Deviation 11.18 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 52 | -3.0 Millimeter of mercury (mmHg) | Standard Deviation 12.33 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 28 | -2.1 Millimeter of mercury (mmHg) | Standard Deviation 8.15 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 52 | -3.8 Millimeter of mercury (mmHg) | Standard Deviation 24.78 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Withdrawal/Study Conclusion | -1.3 Millimeter of mercury (mmHg) | Standard Deviation 15.64 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 56 | -8.2 Millimeter of mercury (mmHg) | Standard Deviation 18.74 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 20 | -11.5 Millimeter of mercury (mmHg) | Standard Deviation 14.69 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, 30 Day Follow-up | 3.2 Millimeter of mercury (mmHg) | Standard Deviation 9.98 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 4 | -3.9 Millimeter of mercury (mmHg) | Standard Deviation 22.76 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 8 | -2.7 Millimeter of mercury (mmHg) | Standard Deviation 24.73 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 12 | -9.3 Millimeter of mercury (mmHg) | Standard Deviation 23.54 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 16 | -7.9 Millimeter of mercury (mmHg) | Standard Deviation 24.43 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 20 | -13.8 Millimeter of mercury (mmHg) | Standard Deviation 25.15 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 24 | -7.8 Millimeter of mercury (mmHg) | Standard Deviation 26.06 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 28 | -5.2 Millimeter of mercury (mmHg) | Standard Deviation 10.71 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 32 | -6.3 Millimeter of mercury (mmHg) | Standard Deviation 5.51 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 36 | -26.7 Millimeter of mercury (mmHg) | Standard Deviation 37.75 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 40 | -34.0 Millimeter of mercury (mmHg) | Standard Deviation 38.18 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 44 | -38.0 Millimeter of mercury (mmHg) | Standard Deviation 32.53 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Week 48 | -84.0 Millimeter of mercury (mmHg) | — |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, Withdrawal/Study Conclusion | 7.0 Millimeter of mercury (mmHg) | Standard Deviation 20.28 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | SBP, 30 Day Follow-up | 13.8 Millimeter of mercury (mmHg) | Standard Deviation 19.25 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 4 | -4.8 Millimeter of mercury (mmHg) | Standard Deviation 11.1 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 8 | -1.2 Millimeter of mercury (mmHg) | Standard Deviation 12.46 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 12 | -4.2 Millimeter of mercury (mmHg) | Standard Deviation 12.87 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 16 | -4.4 Millimeter of mercury (mmHg) | Standard Deviation 15.18 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 20 | -9.1 Millimeter of mercury (mmHg) | Standard Deviation 13.65 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 24 | -5.2 Millimeter of mercury (mmHg) | Standard Deviation 13.08 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 28 | -2.0 Millimeter of mercury (mmHg) | Standard Deviation 5.05 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 32 | -4.7 Millimeter of mercury (mmHg) | Standard Deviation 6.51 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 36 | -10.7 Millimeter of mercury (mmHg) | Standard Deviation 11.02 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 40 | -8.0 Millimeter of mercury (mmHg) | Standard Deviation 19.8 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 44 | -19.5 Millimeter of mercury (mmHg) | Standard Deviation 6.36 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Week 48 | -34.0 Millimeter of mercury (mmHg) | — |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points | DBP, Withdrawal/Study Conclusion | 2.1 Millimeter of mercury (mmHg) | Standard Deviation 8.64 |
Primary
Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Mean/Standard Deviation
Extent of exposure is defined as the duration of the treatment administered during the study. The mean duration of exposure to lapatinib, trastuzumab and paclitaxel is calculated as the number of weeks between the start and end of treatment.
Time frame: From the date of the first dose of the investigational product to end of study, up to approx. 14 years
Population: Safety Population: all participants who were randomized and received at least one dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Mean/Standard Deviation | Trastuzumab | 60.7 Weeks | Standard Deviation 72.07 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Mean/Standard Deviation | Lapatinib | 70.9 Weeks | Standard Deviation 115.44 |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Mean/Standard Deviation | Paclitaxel | 26.9 Weeks | Standard Deviation 16.88 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Mean/Standard Deviation | Trastuzumab | 72.2 Weeks | Standard Deviation 88.66 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Mean/Standard Deviation | Lapatinib | 93.1 Weeks | Standard Deviation 147.92 |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Mean/Standard Deviation | Paclitaxel | 29.4 Weeks | Standard Deviation 23 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Mean/Standard Deviation | Lapatinib | 82.5 Weeks | Standard Deviation 135.79 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Mean/Standard Deviation | Paclitaxel | 23.8 Weeks | Standard Deviation 14.87 |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Mean/Standard Deviation | Trastuzumab | 62.3 Weeks | Standard Deviation 75.52 |
Primary
Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Median/Min-Max
Extent of exposure is defined as the duration of the treatment administered during the study. The mean duration of exposure to lapatinib, trastuzumab and paclitaxel is calculated as the number of weeks between the start and end of treatment.
Time frame: From the date of the first dose of the investigational product to end of study, up to approx. 14 years
Population: Safety Population: all participants who were randomized and received at least one dose of investigational product.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Median/Min-Max | Trastuzumab | 33.0 Weeks |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Median/Min-Max | Lapatinib | 33.0 Weeks |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Median/Min-Max | Paclitaxel | 22.0 Weeks |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Median/Min-Max | Trastuzumab | 37.0 Weeks |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Median/Min-Max | Lapatinib | 38.5 Weeks |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Median/Min-Max | Paclitaxel | 23.5 Weeks |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Median/Min-Max | Lapatinib | 32.5 Weeks |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Median/Min-Max | Paclitaxel | 22.0 Weeks |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Extent of Exposure to Lapatinib, Trastuzumab and Paclitaxel by Median/Min-Max | Trastuzumab | 31.5 Weeks |
Primary
Number of Events of Diarrhea With the Indicated Characteristics
Events of diarrhea are characterized as serious, related to investigational product, leading to withdrawal from the study and fatal. Participants could have been counted in more than one category.
Time frame: From the date of the first dose of investigational product until 30 days after the last dose of investigational product, up to approx. 3.5 years
Population: Safety Population. Only the participants with at least one event of diarrhea were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Diarrhea With the Indicated Characteristics | Leading to withdrawal from study | 2 Events of diarrhea |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Diarrhea With the Indicated Characteristics | Related to investigational product | 347 Events of diarrhea |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Diarrhea With the Indicated Characteristics | Any Event | 358 Events of diarrhea |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Diarrhea With the Indicated Characteristics | Serious | 4 Events of diarrhea |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Diarrhea With the Indicated Characteristics | Fatal | 0 Events of diarrhea |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Diarrhea With the Indicated Characteristics | Related to investigational product | 75 Events of diarrhea |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Diarrhea With the Indicated Characteristics | Any Event | 90 Events of diarrhea |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Diarrhea With the Indicated Characteristics | Serious | 0 Events of diarrhea |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Diarrhea With the Indicated Characteristics | Leading to withdrawal from study | 1 Events of diarrhea |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Diarrhea With the Indicated Characteristics | Fatal | 0 Events of diarrhea |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Diarrhea With the Indicated Characteristics | Fatal | 0 Events of diarrhea |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Diarrhea With the Indicated Characteristics | Leading to withdrawal from study | 1 Events of diarrhea |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Diarrhea With the Indicated Characteristics | Any Event | 37 Events of diarrhea |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Diarrhea With the Indicated Characteristics | Related to investigational product | 26 Events of diarrhea |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Diarrhea With the Indicated Characteristics | Serious | 0 Events of diarrhea |
Primary
Number of Events of Hepatotoxicity With the Indicated Characteristics
Events of hepatotoxicity are characterized as serious, related to investigational product, leading to withdrawal from the study and fatal. Participants could have been counted in more than one category.
Time frame: From the date of the first dose of investigational product until 30 days after the last dose of investigational product, up to approx. 3.5 years
Population: Safety Population. Only the participants with at least one of event of hepatotoxicity were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Hepatotoxicity With the Indicated Characteristics | Serious | 0 Events of hepatotoxicity |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Hepatotoxicity With the Indicated Characteristics | Leading to withdrawal from study | 0 Events of hepatotoxicity |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Hepatotoxicity With the Indicated Characteristics | Related to investigational product | 5 Events of hepatotoxicity |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Hepatotoxicity With the Indicated Characteristics | Fatal | 0 Events of hepatotoxicity |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Hepatotoxicity With the Indicated Characteristics | Any Event | 6 Events of hepatotoxicity |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Hepatotoxicity With the Indicated Characteristics | Fatal | 0 Events of hepatotoxicity |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Hepatotoxicity With the Indicated Characteristics | Any Event | 2 Events of hepatotoxicity |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Hepatotoxicity With the Indicated Characteristics | Serious | 0 Events of hepatotoxicity |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Hepatotoxicity With the Indicated Characteristics | Related to investigational product | 0 Events of hepatotoxicity |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Hepatotoxicity With the Indicated Characteristics | Leading to withdrawal from study | 0 Events of hepatotoxicity |
Primary
Number of Events of Rash With the Indicated Characteristics
Events of rash are characterized as serious, related to investigational product, leading to withdrawal from the study and fatal. Participants could have been counted in more than one category.
Time frame: From the date of the first dose of investigational product until 30 days after the last dose of investigational product, up to approx. 3.5 years
Population: Safety Population. Only the participants with at least one event of rash were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Rash With the Indicated Characteristics | Any Event | 69 Events of rash |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Rash With the Indicated Characteristics | Leading to withdrawal from study | 3 Events of rash |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Rash With the Indicated Characteristics | Related to investigational product | 55 Events of rash |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Rash With the Indicated Characteristics | Fatal | 0 Events of rash |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Rash With the Indicated Characteristics | Serious | 2 Events of rash |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Rash With the Indicated Characteristics | Fatal | 0 Events of rash |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Rash With the Indicated Characteristics | Any Event | 23 Events of rash |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Rash With the Indicated Characteristics | Serious | 0 Events of rash |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Rash With the Indicated Characteristics | Related to investigational product | 12 Events of rash |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Events of Rash With the Indicated Characteristics | Leading to withdrawal from study | 0 Events of rash |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Rash With the Indicated Characteristics | Serious | 0 Events of rash |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Rash With the Indicated Characteristics | Fatal | 0 Events of rash |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Rash With the Indicated Characteristics | Leading to withdrawal from study | 0 Events of rash |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Rash With the Indicated Characteristics | Any Event | 20 Events of rash |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Events of Rash With the Indicated Characteristics | Related to investigational product | 7 Events of rash |
Primary
Number of Participants Who Died Due to Any Cause
Number of participants who died due to any cause throughout the study including off-treatment deaths (on-treatment deaths are reported for the All-Cause Mortality in the AE section).
Time frame: From the date of the first dose of investigational product until last patient last visit, up to approximately 14 years
Population: Safety Population: all participants who were randomized and received at least one dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants Who Died Due to Any Cause | 12 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants Who Died Due to Any Cause | 2 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants Who Died Due to Any Cause | 1 Participants |
Primary
Number of Participants Who Received Any Concomitant Medications During the Study Period
Number of participants who received any concomitant medication along with study drugs (lapatinib, trastuzumab and paclitaxel) were counted during the treatment period.
Time frame: withdrawal/study completion, up to approx. 3.5 years
Population: Safety Population: all participants who were randomized and received at least one dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants Who Received Any Concomitant Medications During the Study Period | 29 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants Who Received Any Concomitant Medications During the Study Period | 14 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants Who Received Any Concomitant Medications During the Study Period | 20 Participants |
Primary
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations. Refer to the general AE/SAE module for a list of non-serious AEs and SAEs.
Time frame: From the date of the first dose of investigational product until 30 days after the last dose of investigational product, up to approx. 14 years
Population: Safety Population: all participants who were randomized and received at least one dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AEs | 29 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAEs | 14 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AEs | 14 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAEs | 6 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AEs | 20 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAEs | 5 Participants |
Primary
Number of Participants With at Least 1 Event of Left Ventricular Ejection Fraction Decrease With the Indicated Characteristics
Events of left ventricular ejection fraction (LVEF) decrease were based on the number of participants who had an actual event and was characterized as serious, related to investigational product, leading to withdrawal from the study and/or fatal.
Time frame: Baseline and every 8 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years
Population: Safety Population. Only the participants with at least one of event of LVEF decrease were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With at Least 1 Event of Left Ventricular Ejection Fraction Decrease With the Indicated Characteristics | 8 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With at Least 1 Event of Left Ventricular Ejection Fraction Decrease With the Indicated Characteristics | 2 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With at Least 1 Event of Left Ventricular Ejection Fraction Decrease With the Indicated Characteristics | 0 Participants |
Primary
Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value
The Eastern Cooperative Oncology Group (ECOG) performance status scales and grades/criteria are used to assess how a participant's disease is progressing, to assess how the disease affects the daily living abilities of the participant, and to determine appropriate treatment and prognosis. Grade 0, fully active, able to carry on all pre-disease performance without restriction. Grade 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. Grade 2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about more than 50% of waking hours. Grade 3, capable of only limited selfcare; confined to bed or chair more than 50% of waking hours. Grade 4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. Grade 5, dead.
Time frame: Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years
Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 88, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 12, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 12, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 12, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 16, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 16, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 16, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 20, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 20, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 20, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 24, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 24, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 24, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 28, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 28, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 28, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 32, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 32, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 32, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 36, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 36, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 36, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 40, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 40, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 40, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 44, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 44, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 44, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 48, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 48, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 48, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 52, Grade3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 52, Grade4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 52, Grade5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 56, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 56, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 56, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 60, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 60, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 60, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 64, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 64, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 64, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 68, Grade3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 68, Grade4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 68, Grade5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 72, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 72, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 72, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 76, Grade3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 76, Grade4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 76, Grade5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 80, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 80, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 80, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 84, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 84, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 84, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Screening, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 88, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 88, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 92, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 92, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 92, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 96, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 96, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 96, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 100, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 100, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 100, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 104, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 104, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 104, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 108, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 108, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 108, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 112, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 112, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 112, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 116, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 116, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 116, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 120, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 120, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 120, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 124, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 124, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 124, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 128, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 128, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 128, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 132, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 132, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 132, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 136, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 136, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 136, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 140, Grade 3 | 2 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 140, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 140, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 144, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 144, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 144, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 148, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 148, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 148, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal/Study conclusion, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal/Study conclusion, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal/Study conclusion, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Screening, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Screening, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Day 1 pre-dose, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Day 1 pre-dose, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Day 1 pre-dose, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, Grade 5 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 8, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 8, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 8, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Screening, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 72, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 12, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 48, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 12, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 12, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 64, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 16, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 48, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 16, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 16, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal/Study conclusion, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 20, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 52, Grade3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 20, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 68, Grade3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 20, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 52, Grade4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 24, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal/Study conclusion, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 24, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 52, Grade5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 24, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 68, Grade4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 28, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 56, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 28, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 28, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 56, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 32, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 68, Grade5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 32, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 56, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 32, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 36, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 60, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 36, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 72, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 36, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 60, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 40, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal/Study conclusion, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 40, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 60, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 40, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 72, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 44, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Screening, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Screening, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 64, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Day 1 pre-dose, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 44, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Day 1 pre-dose, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Day 1 pre-dose, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 44, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, Grade 5 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 64, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 8, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 48, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 8, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 8, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Screening, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 16, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 24, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Screening, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 44, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 32, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Screening, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 16, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 48, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Day 1 pre-dose, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 36, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 16, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Day 1 pre-dose, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 44, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 28, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Day 1 pre-dose, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal/Study conclusion, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 40, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 20, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 32, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 44, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 28, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 4, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 20, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal/Study conclusion, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 8, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Withdrawal/Study conclusion, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 20, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 8, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 48, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 28, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 8, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 40, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 24, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 12, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 36, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 32, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 12, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 48, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 24, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 12, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 36, Grade 5 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status Value | Week 40, Grade 4 | 0 Participants |
Primary
Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters
Blood samples for clinical laboratory evaluation were taken at Baseline prior to the administration of investigational product and thereafter at each scheduled visit. Clinical chemistry parameters included values \> upper limit of normal (ULN)=Hyper; values \< lower limit of normal (LLN)=Hypo of sodium (Hypernatraemia and Hyponatraemia), potassium (Hyperkalaemia and Hypokalaemia), calcium (Hypercalcaemia and Hypocalcaemia), glucose (Hyperglycaemia and Hyperglycaemia), creatinine (if \>2 milligram per deciliter \[mg/dL\]), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phophatase, total bilirubin (if available bilirubin fractionation is recommended if the total bilirubin is \> twice of ULN), and albumin. Clinical chemistry data was summarized by National Cancer Institute's Common toxicity criteria for adverse events (NCI CTCAE) toxicity grade (Version 3.0). Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling; Grade 5, death.
Time frame: Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypocalcaemia, Grade 3 | 3 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperkalaemia, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperkalaemia, Grade 4 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypokalaemia, Grade 1 | 11 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypokalaemia, Grade 2 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypokalaemia, Grade 3 | 6 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypernatraemia, Grade 2 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypokalaemia, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypercalcaemia, Grade 1 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypercalcaemia, Grade 2 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypercalcaemia, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypercalcaemia, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypocalcaemia, Grade 1 | 10 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypocalcaemia, Grade 2 | 7 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypernatraemia, Grade 1 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypocalcaemia, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperglycaemia, Grade 1 | 15 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperglycaemia, Grade 2 | 3 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperglycaemia, Grade 3 | 5 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperglycaemia, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypoglycemia, Grade 1 | 5 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypoglycemia, Grade 2 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypoglycemia, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypoglycemia, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Albumin, Grade 1 | 5 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Albumin, Grade 2 | 3 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Albumin, Grade 3 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Albumin, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Total Bilirubin, Grade 1 | 2 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Total Bilirubin, Grade 2 | 2 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Total Bilirubin, Grade 3 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Total Bilirubin, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Creatinine, Grade 1 | 2 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Creatinine, Grade 2 | 2 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Creatinine, Grade 3 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Creatinine, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Alkaline Phophatase, Grade 1 | 14 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Alkaline Phophatase, Grade 2 | 2 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Alkaline Phophatase, Grade 3 | 2 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Alkaline Phophatase, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | ALT, Grade 1 | 7 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | ALT, Grade 2 | 3 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | ALT, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | ALT, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | AST, Grade 1 | 6 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | AST, Grade 2 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | AST, Grade 3 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | AST, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypernatraemia, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypernatraemia, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyponatraemia, Grade 1 | 8 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyponatraemia, Grade 2 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyponatraemia, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyponatraemia, Grade 4 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperkalaemia, Grade 1 | 2 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperkalaemia, Grade 2 | 2 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | ALT, Grade 1 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperglycaemia, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypoglycemia, Grade 1 | 2 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | AST, Grade 1 | 3 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypoglycemia, Grade 2 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypoglycemia, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyponatraemia, Grade 3 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypoglycemia, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | AST, Grade 2 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Albumin, Grade 1 | 3 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Albumin, Grade 2 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Albumin, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | AST, Grade 3 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Albumin, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Total Bilirubin, Grade 1 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Total Bilirubin, Grade 2 | 2 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | AST, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Total Bilirubin, Grade 3 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Total Bilirubin, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyponatraemia, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Creatinine, Grade 1 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypernatraemia, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Creatinine, Grade 2 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Creatinine, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Creatinine, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypernatraemia, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Alkaline Phophatase, Grade 1 | 3 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Alkaline Phophatase, Grade 2 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperkalaemia, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperkalaemia, Grade 2 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperkalaemia, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Alkaline Phophatase, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypokalaemia, Grade 1 | 6 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypokalaemia, Grade 2 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyponatraemia, Grade 1 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypokalaemia, Grade 3 | 2 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypernatraemia, Grade 1 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Alkaline Phophatase, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypernatraemia, Grade 2 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypokalaemia, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypercalcaemia, Grade 1 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypercalcaemia, Grade 2 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypercalcaemia, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperkalaemia, Grade 1 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypercalcaemia, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | ALT, Grade 2 | 3 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypocalcaemia, Grade 1 | 3 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypocalcaemia, Grade 2 | 2 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyponatraemia, Grade 2 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypocalcaemia, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | ALT, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypocalcaemia, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperglycaemia, Grade 1 | 9 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperglycaemia, Grade 2 | 3 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | ALT, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperglycaemia, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperglycaemia, Grade 3 | 2 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | ALT, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Alkaline Phophatase, Grade 2 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperglycaemia, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperkalaemia, Grade 1 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypocalcaemia, Grade 2 | 3 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypoglycemia, Grade 1 | 2 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperkalaemia, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypercalcaemia, Grade 2 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypoglycemia, Grade 2 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | AST, Grade 1 | 6 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | ALT, Grade 1 | 3 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypoglycemia, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperkalaemia, Grade 4 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | ALT, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypoglycemia, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypercalcaemia, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypokalaemia, Grade 1 | 6 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Albumin, Grade 1 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | AST, Grade 2 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Alkaline Phophatase, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Albumin, Grade 2 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyponatraemia, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperglycaemia, Grade 2 | 2 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Albumin, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypokalaemia, Grade 2 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypocalcaemia, Grade 3 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Albumin, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | AST, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypercalcaemia, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Total Bilirubin, Grade 1 | 3 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperkalaemia, Grade 2 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyperglycaemia, Grade 1 | 6 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Total Bilirubin, Grade 2 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypernatraemia, Grade 1 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyponatraemia, Grade 2 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Total Bilirubin, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | AST, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypocalcaemia, Grade 1 | 4 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Total Bilirubin, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypernatraemia, Grade 2 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypokalaemia, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Creatinine, Grade 1 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Alkaline Phophatase, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | ALT, Grade 2 | 2 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Creatinine, Grade 2 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypernatraemia, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypokalaemia, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Creatinine, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyponatraemia, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hyponatraemia, Grade 1 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Creatinine, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypocalcaemia, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypercalcaemia, Grade 1 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Alkaline Phophatase, Grade 1 | 5 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters | Hypernatraemia, Grade 4 | 0 Participants |
Primary
Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters
Blood samples for clinical laboratory evaluation were taken at Baseline prior to the administration of investigational product and thereafter at each scheduled visit. Haematology parameters included haemoglobin, total white blood cell count (WBC), neutrophils, lymphocytes and platelets. Hematology data was summarized by the National Cancer Institute's Common toxicity criteria for adverse events (NCI CTCAE) toxicity grade (Version 3.0). Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling; Grade 5, death.
Time frame: Baseline and every 4 weeks thereafter up to withdrawal/study completion and 30 day follow-up, up to approx. 3.5 years
Population: Safety Population: all participants who were randomized and received at least one dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Lymphocytes, Grade 3 | 5 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Neutrophils, Grade 1 | 7 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Total WBC, Grade 2 | 8 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Platelets, Grade 1 | 3 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Haemaglobin, Grade 2 | 7 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Total WBC, Grade 3 | 3 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Lymphocytes, Grade 4 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Haemaglobin, Grade 1 | 19 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Total WBC, Grade 4 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Neutrophils, Grade 4 | 3 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Platelets, Grade 2 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Haemaglobin, Grade 4 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Neutrophils, Grade 3 | 3 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Platelets, Grade 3 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Lymphocytes, Grade 2 | 10 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Neutrophils, Grade 2 | 7 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Platelets, Grade 4 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Haemaglobin, Grade 3 | 2 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Lymphocytes, Grade 1 | 5 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Total WBC, Grade 1 | 10 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Platelets, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Haemaglobin, Grade 3 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Haemaglobin, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Platelets, Grade 1 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Platelets, Grade 2 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Platelets, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Total WBC, Grade 1 | 6 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Total WBC, Grade 2 | 4 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Total WBC, Grade 3 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Total WBC, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Haemaglobin, Grade 1 | 11 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Haemaglobin, Grade 2 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Neutrophils, Grade 1 | 2 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Neutrophils, Grade 2 | 4 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Lymphocytes, Grade 1 | 3 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Lymphocytes, Grade 2 | 4 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Neutrophils, Grade 3 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Neutrophils, Grade 4 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Lymphocytes, Grade 3 | 3 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Lymphocytes, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Platelets, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Platelets, Grade 3 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Haemaglobin, Grade 3 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Haemaglobin, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Neutrophils, Grade 2 | 4 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Lymphocytes, Grade 1 | 7 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Neutrophils, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Lymphocytes, Grade 4 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Platelets, Grade 2 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Lymphocytes, Grade 3 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Total WBC, Grade 3 | 4 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Neutrophils, Grade 3 | 5 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Haemaglobin, Grade 1 | 11 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Total WBC, Grade 2 | 2 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Platelets, Grade 1 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Haemaglobin, Grade 2 | 6 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Total WBC, Grade 4 | 0 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Total WBC, Grade 1 | 7 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Lymphocytes, Grade 2 | 4 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Hematology Parameters | Neutrophils, Grade 1 | 5 Participants |
Primary
Overall Response (OR): Percentage of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator
OR is defined as the number of participants achieving either a CR or PR, per Response Evaluation Criteria in Solid Tumors (RECIST). The best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made \>=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.
Time frame: From the date of the first dose of investigational product to end of study, up to approx. 7 years
Population: Safety Population: all participants who were randomized and received at least one dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Overall Response (OR): Percentage of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator | 79.3 Percentage of participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Overall Response (OR): Percentage of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator | 71.4 Percentage of participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Overall Response (OR): Percentage of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator | 70.0 Percentage of participants |
Secondary
Duration of Response (DoR), as Assessed by the Investigator
DoR is defined for the subset of participants who had a confirmed CR (disappearance of all TLs and non-TLs) or PR (\>=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL\[s\]) as the time from the first documented evidence of a CR or PR until the first documentation of radiological PD or death due to breast cancer, if sooner. PD is defined as \>=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. For participants who did not progress or die, DoR was censored on the date of the last radiological scan. If a participant had only a Baseline visit or did not have a date of a radiological scan that was later than the date of initiation of anti-cancer therapy, DoR was censored at the start date of treatment.
Time frame: From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer, up to approx. 7 years
Population: Safety Population. Safety Population: all participants who were randomized and received at least one dose of investigational product. Only those participants with CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Duration of Response (DoR), as Assessed by the Investigator | 56.6 Weeks |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Duration of Response (DoR), as Assessed by the Investigator | 59.0 Weeks |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Duration of Response (DoR), as Assessed by the Investigator | 70.6 Weeks |
Secondary
Percentage of Participants With Clinical Benefit (Complete Response (CR), Partial Response (PR), and Stable Disease [SD] for at Least 24 Weeks) as Assessed by Investigator
Clinical benefit is defined as the percentage of participants achieving either a CR or PR or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of the LD of target lesions, taking as a reference, the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions), taking as reference, the smallest sum LD since the treatment started) for at least 24 weeks. This was based on confirmed responses from the investigator assessment of clinical benefit.
Time frame: From the date of the first dose of investigational product until the first documented evidence of a PR or CR or SD until the earlier of the date of disease progression or the date of death due to breast cancer, up to approx. 7 years
Population: Safety Population. Safety Population: all participants who were randomized and received at least one dose of investigational product. Only those participants with CR, PR and SD for at least 24 weeks were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Percentage of Participants With Clinical Benefit (Complete Response (CR), Partial Response (PR), and Stable Disease [SD] for at Least 24 Weeks) as Assessed by Investigator | 79.3 Percentage of Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Percentage of Participants With Clinical Benefit (Complete Response (CR), Partial Response (PR), and Stable Disease [SD] for at Least 24 Weeks) as Assessed by Investigator | 71.4 Percentage of Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Percentage of Participants With Clinical Benefit (Complete Response (CR), Partial Response (PR), and Stable Disease [SD] for at Least 24 Weeks) as Assessed by Investigator | 70.0 Percentage of Participants |
Secondary
Progression-free Survival as Assessed by the Investigator
Progression-free survival is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. Disease progression was based on the investigator's assessments of the objective evidence (e.g., radiological scans and medical photographs). For participants who do not progress, or die, progression-free survival was censored at the time of the last investigator assessed radiological scan preceding the initiation of any alternative anti-cancer therapy. Progression-free survival was summarized using Kaplan-Meier curves.
Time frame: From the date of the first dose of investigational product until the earlier of the date of disease progression or death due to any cause, up to approx. 7 years
Population: Safety Population: all participants who were randomized and received at least one dose of investigational product. Only those participants with CR, PR and SD for at least 24 weeks were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Progression-free Survival as Assessed by the Investigator | 64.7 Weeks |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Progression-free Survival as Assessed by the Investigator | 55.0 Weeks |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Progression-free Survival as Assessed by the Investigator | 78.4 Weeks |
Secondary
Time to Response as Assessed by the Investigator
Time to Response was defined for subjects who had a confirmed CR or PR as the time from first dose until first documented evidence of partial or complete tumour response (whichever status was recorded first). CR is defined as the disappearance of all TLs & non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s). PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs.
Time frame: From the date of the first dose of investigational product until the first documented evidence of a PR or CR, up to approx. 7 years
Population: Safety Population. Safety Population: all participants who were randomized and received at least one dose of investigational product. Only those participants with CR or PR were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Time to Response as Assessed by the Investigator | Week 8 | 15 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Time to Response as Assessed by the Investigator | Week 12 | 5 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Time to Response as Assessed by the Investigator | Week 16 | 2 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Time to Response as Assessed by the Investigator | Week 20 | 0 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Time to Response as Assessed by the Investigator | Week 24 | 1 Participants |
| Cohort 1: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Time to Response as Assessed by the Investigator | Week 28 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Time to Response as Assessed by the Investigator | Week 28 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Time to Response as Assessed by the Investigator | Week 8 | 8 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Time to Response as Assessed by the Investigator | Week 20 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Time to Response as Assessed by the Investigator | Week 24 | 0 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Time to Response as Assessed by the Investigator | Week 12 | 1 Participants |
| Cohort 2: Paclitaxel 70 mg/Trastuzumab 4 mg/Lapatinib 1000 mg | Time to Response as Assessed by the Investigator | Week 16 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Time to Response as Assessed by the Investigator | Week 12 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Time to Response as Assessed by the Investigator | Week 16 | 3 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Time to Response as Assessed by the Investigator | Week 28 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Time to Response as Assessed by the Investigator | Week 20 | 1 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Time to Response as Assessed by the Investigator | Week 8 | 8 Participants |
| Cohort 3: Paclitaxel 80 mg/Trastuzumab 4 mg/Lapatinib 750 mg | Time to Response as Assessed by the Investigator | Week 24 | 0 Participants |