Neoplasms, Breast
Conditions
Keywords
Lapatinib, ErbB2+, Early Breast Cancer, Neoadjuvant, breast carcinoma, breast cancer, breast lump, HER2 positive metastatic breast cancer, breast cancer positive for human epidermal growth factor receptor 2 (HER2) HER2 positive metastatic breast cancer, breast cancer progression, estrogen-receptor (ER) positive(+) breast cancer, Paget's disease
Brief summary
This is a randomised, open label multicenter Phase III study comparing the efficacy of neoadjuvant lapatinib plus paclitaxel, versus trastuzumab plus paclitaxel, versus concomitant lapatinib and trastuzumab plus paclitaxel given as neoadjuvant treatment in HER2/ErbB2 over-expressing and/or amplified primary breast cancer. Patients will be randomised to receive either: lapatinib 1500 mg daily, trastuzumab 4 mg/kg intravenous (IV) load followed by 2 mg/kg IV weekly, or lapatinib 1000 mg daily with trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for a total of 6 weeks. After this biological window, patients on monotherapy arms will continue on the same targeted therapy plus weekly paclitaxel 80 mg/m\^2 for a further 12 weeks, up to definitive surgery. In the combination arm, patients will receive lapatinib 750 mg daily in combination with trastuzumab 2 mg/kg IV plus weekly paclitaxel 80mg/m\^2 IV for a further 12 weeks, up to definitive surgery. After surgery, patients will receive three courses of adjuvant chemotherapy with 5-Fluorouracil Epirubicin Cyclophosphamide (FEC) followed by the same targeted therapy as in the biological window of the neoadjuvant setting for a further 34 weeks (in the combination arm, lapatinib dose will be 1000 mg daily in combination with trastuzumab). The planned total duration of the anti-HER2 therapy one year. Primary objective is to evaluate and compare the rate of pathological complete response (pCR) at the time of surgery in patients with HER2/ErbB2 overexpressing or amplified operable breast cancer randomised to lapatinib followed by lapatinib plus paclitaxel versus trastuzumab followed by trastuzumab plus paclitaxel versus lapatinib in combination with trastuzumab followed by lapatinib, trastuzumab plus paclitaxel.
Detailed description
This was a parallel group, three-arm, randomized, multicenter, open-label phase III study. The study compared the efficacy and tolerability of neoadjuvant lapatinib and paclitaxel, versus trastuzumab and paclitaxel, versus the combination of lapatinib with trastuzumab and paclitaxel given as neoadjuvant treatment in HER2/ErbB2 over-expressing and/or amplified primary breast cancer. Subjects were randomized to receive lapatinib, trastuzumab or lapatinib plus trastuzumab for a total of 6 weeks. After this biological window, subjects continued on the same targeted therapy plus weekly paclitaxel for a further 12 weeks, until definitive surgery (total neoadjuvant therapy duration of 18 weeks). Paclitaxel could be initiated at Week 4 if there is evidence of progressive disease (PD) at that time. Within 6 weeks after surgery, subjects received 3 cycles of adjuvant 5-flourouracil, epirubicin and cyclophosphamide (FEC) followed by the same targeted therapy as in the biological window of the neoadjuvant phase for a further 34 weeks (to complete 52 weeks of anti-HER2 therapy). After completing 52 weeks of (neo-)/adjuvant anti-HER2 therapy, subjects were scheduled to attend post-treatment follow-up every 3 months during the first year (months 12, 15, 18, 21, and 24), every 6months in Years 3 to 5 inclusive, and annually thereafter up to Year 10. Each subject was to be followed for 10 Years. All subjects were to be followed for EFS and OS up to 10 years from last subject randomized.
Interventions
DRUGLapatinib
Small molecule receptor tyrosine kinase inhibitor
BIOLOGICALTrastuzumab
Therapeutic Monoclonal Antibody
DRUGPaclitaxel
antimicrotubule agent
Sponsors
Breast International Group
SOLTI Breast Cancer Research Group
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female gender; * Age ≥18 years; * Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1 * Histologically confirmed invasive breast cancer: * Primary tumour greater than 2 cm diameter, measured by clinical examination and mammography or echography, * Any N, * No evidence of metastasis (M0) (isolated supraclavicular node involvement allowed); * Over expression and/or amplification of HER2 in the invasive component of the primary tumour \[Wolff et al 2006\] and confirmed by a certified laboratory prior to randomisation * Known hormone receptor status. * Haematopoietic status: * Absolute neutrophil count ≥ 1,5 x 10\^9/L, * Platelet count ≥ 100 x 10\^9/L, * Hemoglobin at least 9 g/dl, * Hepatic status: * Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN). In the case of known Gilbert's syndrome, a higher serum total bilirubin (\< 2 x ULN) is allowed, * Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times ULN, * Alkaline phosphatase ≤ 2.5 times ULN, * Renal status: * Creatinine ≤ 2.0 mg/dL, * Cardiovascular: * Baseline left ventricular ejection fraction (LVEF) ³ 50% measured by echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan, * Negative serum pregnancy test, within 2-weeks (preferably 7 days) prior to randomization (For women of childbearing potential) * Fertile patients must use effective contraception (barrier method - condoms, diaphragm - also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed) * Signed informed consent form (ICF) * Patient accepts to make available tumour samples for submission to central laboratory to conduct translational studies as part of this protocol
Exclusion criteria
* Received any prior treatment for primary invasive breast cancer; * Previous (less than 10 years) or current history of malignant neoplasms, except for curatively treated: * Basal and squamous cell carcinoma of the skin; * Carcinoma in situ of the cervix. * Patients with a prior malignancy diagnosed more than 10 years prior to randomisation may enter the study. Patients must have been curatively treated with surgery alone. Radiation therapy or systemic therapy (chemotherapy or endocrine) are NOT permitted. Prior diagnoses of breast cancer or melanoma are excluded. * Diagnosis of inflammatory breast cancer; * Bilateral cancer; * This criterion has been deleted from the protocol Version 1. Patients with multi-focal cancer are no longer excluded. * Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnoea at rest, or chronic therapy with oxygen; * Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety; * Unresolved or unstable, serious adverse events from prior administration of another investigational drug; * Active or uncontrolled infection; * Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF; * Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded; * Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy other than the trial therapies); * Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial; * Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trastuzumab or lapatinib or their excipients; * Pregnant or lactating women; * Concomitant use of CYP3A4 inhibitors or inducers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Pathological Complete Response (pCR) at the Time of Surgery | Weeks 20 to 22 | Pathological complete response is defined as no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. Surgical breast and axillary node resection specimens were evaluated for pathologic tumor response according to National Surgical Adjuvant Breast and Bowel Project (NSABP) guidelines, which do not take into account the histological nodal status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response at the Time of Surgery | Time of surgery (Weeks 20 to 22) | The number of participants with overall response (complete response and/or partial response) was evaluated using WHO criteria by clinical examination and mammography and breast echography with bi-dimensional measurements at the time of surgery (Weeks 20 to 22). As per WHO criteria: complete response is defined as the disappearance of all lesions; partial response is defined as a greater than 50% decrease in the sum of products of the greatest length and width of the largest lesion; progressive disease is defined as a greater than 25% increase in the sum of products of all measurable lesions. |
| Number of Participants With Negative Lymph Nodes at the Time of Surgery | Time of surgery (Weeks 20 to 22) | Participants were assessed for node-negative lymph nodes at the time of surgery. As per the pathological TNM (Tumor, Node, Metastases) classification (pTNM) of malignant tumors: pN, absence or presence and extent of regional lymph node metastasis. Node-negative (pN0) participants had no regional lymph node metastasis. Although not assessed in this measure, pT is the extent of primary tumor, and pM is the absence or presence of distant metastasis. |
| Number of Participants With Actual Indicated Surgery | At surgery (Weeks 20 to 22) | Participants were assessed for the type of surgery they underwent for breast cancer. Non-conservative surgery is defined as a radical or modified radical mastectomy. Conservative surgery is comprised of a lumpectomy, a quadrantectomy/segmentectomy, or a partial mastectomy. Participants who were not assessed as being candidates for non-conservative or conservative surgery were classified as non-operable. |
| Mean Change From Baseline in Tumor Size at Week 6 and at Surgery | Week 6 and surgery (Weeks 20 to 22) | Mean change from baseline in tumor in tumor size. Change from baseline in tumor size was defined as tumor size at Week 6/ surgery (Weeks 20 to 22) minus tumor size at baseline. The difference in treatment arms was estimated for Lapatinib 1500 mg versus Trastuzumab 2 mg/kg and for Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg versus Trastuzumab 2 mg/kg. |
| Number of Participants Starting Paclitaxel Before Completing 6 Weeks of Treatment With Either Lapatinib or Trastuzumab | Week 6 | Participants with progressive disease at 4 week assessment that were permitted to commence treatment with paclitaxel. |
| Event-free Survival (EFS) - Median Clinical Follow-up | From randomization up to approximately year 10 | Event free survival (EFS) is defined as the time from randomization to first EFS event. For subjects who had breast cancer surgery, EFS events were post-surgery breast cancer relapse, second primary malignancy or death without recurrence. For subjects who did not have breast cancer surgery, EFS events were death during clinical follow-up or non-completion of any neoadjuvant investigational product due to disease progression. |
| Event-free Survival (EFS) - Events and Censoring | From randomization up to approximately year 10 | Event free survival (EFS) is defined as the time from randomization to first EFS event. For subjects who had breast cancer surgery, EFS events were post-surgery breast cancer relapse, second primary malignancy or death without recurrence. For subjects who did not have breast cancer surgery, EFS events were death during clinical follow-up or non-completion of any neoadjuvant investigational product due to disease progression. |
| Overall Survival (OS) - Median Survival Follow-up | From randomization up to approximately year 10 | Overall survival is defined as the period from randomization until death (from any cause). OS was assessed annually for up to 10 years after the randomization of the last participant into the study. |
| Overall Survival (OS) - Deaths and Censoring | From randomization up to approximately year 10 | Overall survival is defined as the period from randomization until death (from any cause). OS was assessed annually for up to 10 years after the randomization of the last participant into the study. |
| Number of Participants With Overall Response at Week 6 | Week 6 | The number of participants with overall response (complete response and/or partial response) was evaluated using World Health Organization (WHO) criteria by clinical examination and by mammography and breast echography with bi-dimensional measurements at Week 6. As per WHO criteria: complete response is defined as the disappearance of all lesions; partial response is defined as a greater than 50% decrease in the sum of products of the greatest length and width of the largest lesion; progressive disease is defined as a greater than 25% increase in the sum of products of all measurable lesions. |
| Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population) | up to year 10 | The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis. For patients who had breast cancer surgery, EFS events are post-surgery breast cancer relapse, second primary malignancy or death without recurrence. For patients who do not undergo breast cancer surgery, EFS events are death during clinical follow-up or non-completion of any neo-adjuvant investigational product due to disease progression or second primary malignancy or contralateral breast cancer. |
| Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population) | up to year 10 | The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis. Patients are considered in survival follow-up from randomisation until one of the following occurs: lost to follow-up, withdrawal of consent, end of follow-up due to completion of year 10 visit, termination of study follow-up, or death. For subjects with no death recorded in the database, time to death is censored. |
| Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population) | up to year 10 | The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis. Includes deaths due to any cause. |
| To Assess Safety Via a Comparison of the Three Treatment Arms - to Measure On-treatment Primary Cardiac Endpoints | Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of 31 weeks. | — |
| Metabolic Response Rate Determined by Positron Emission Tomography/Computed Tomography (PET/CT) | Week 2 and Week 6 | Metabolic Response Rate determined by Positron Emission Tomography/Computed Tomography (PET/CT) |
| Percentage of Participants With the Indicated Biomarker Expression - PIK3CA. | Baseline | Biomarker levels of phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) were assessed in participants at baseline. |
| Percentage of Participants With the Indicated Biomarker Expression - PTEN. | Baseline | Biomarker levels of phosphate and tensin homolog deleted from chromosome 10 (PTEN) were assessed in participants at baseline. |
| Ratio (95% CI) of Geometric Means in p95HER2 Expression in HR Positive Patients With pCR vs no pCR | Baseline | Ratio (95% CI) of geometric means in p95 human epidermal growth factor receptor (p95HER2) expression in hormone-receptor (HR) positive patients with pathological complete response (pCR) vs no pCR |
| Percentage of Participants With Circulating Tumor Cells (CTC) in the Bloodstream | Measurement performed at one or more of the time points: baseline, week 2 or week 18 | Circulating tumor cells (CTCs) are cells that have detached from a primary tumor and circulate in the bloodstream. In the adjuvant phase, after surgery all participants received 3 courses of adjuvant 5-fluorouracil, epirubicin and cyclophosphamide, followed by lapatinib 1500 mg or trastuzumab 2 mg/kg or lapatinib 1000/750 mg plus trastuzumab 2 mg/kg given prior to surgery in the neoadjuvant setting for an additional 34 weeks. |
| Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population) | up to year 10 | The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis. Clinical follow-up is the period during which the patient is monitored such that all recurrence or second primary malignancy (SPM) or contralateral breast cancer (CBC) events would be reported. Patients are considered in clinical follow-up from randomisation until one of the following occurs: lost to follow-up, withdrawal of consent, end of follow-up due to completion of year 10 visit, termination of study follow-up, or death. |
Countries
Argentina, Belgium, Brazil, Canada, Czechia, France, Germany, Hong Kong, Hungary, India, Italy, Lithuania, Norway, Pakistan, Peru, Romania, Russia, South Africa, South Korea, Spain, Sweden, Taiwan, Ukraine, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lapatinib 1500 mg Oral lapatinib (1500 milligrams \[mg\] daily) for 6 weeks, followed by lapatinib plus weekly paclitaxel (80 mg per meters squared \[mg/m\^2\]) intravenous (IV) for an additional 12 weeks | 154 |
| Trastuzumab 2 mg/kg Trastuzumab (4 mg/kilograms \[kg\] IV load followed by 2 mg/kg IV weekly) for 6 weeks, followed by trastuzumab plus weekly paclitaxel (80 mg/m\^2 IV) for an additional 12 weeks | 149 |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg Oral lapatinib 1000 mg daily plus trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV weekly for 6 weeks, followed by lapatinib 750 mg daily plus trastuzumab (2 mg/kg IV weekly) plus weekly paclitaxel (80 mg/m\^2 IV) for an additional 12 weeks | 152 |
| Total | 455 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Died after clinical follow-up ended | 1 | 2 | 0 |
| Overall Study | Died during clinical follow-up | 25 | 29 | 32 |
| Overall Study | Lost to Follow-up | 22 | 26 | 18 |
| Overall Study | Not dead but were last followed-up prior to 9 years + 6 months after randomization | 4 | 2 | 2 |
| Overall Study | Randomized but did not receive treatment | 3 | 3 | 1 |
| Overall Study | Withdrew completely | 23 | 33 | 34 |
| Overall Study | Withdrew (survival only) - alive at end of survival follow-up | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Lapatinib 1500 mg | Total | Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Trastuzumab 2 mg/kg |
|---|---|---|---|---|
| Age, Continuous | 50.0 Years | 50.0 Years | 50.0 Years | 49.0 Years |
| Number of participants with lymph nodes (LNs) of the indicated clinical N stage N0 | 34 Participants | 123 Participants | 48 Participants | 41 Participants |
| Number of participants with lymph nodes (LNs) of the indicated clinical N stage N1 | 95 Participants | 260 Participants | 80 Participants | 85 Participants |
| Number of participants with lymph nodes (LNs) of the indicated clinical N stage N2 (including N2a and N2b) | 19 Participants | 47 Participants | 15 Participants | 13 Participants |
| Number of participants with lymph nodes (LNs) of the indicated clinical N stage N3 (including N3a, N3b, and N3c) | 6 Participants | 19 Participants | 6 Participants | 7 Participants |
| Number of participants with lymph nodes (LNs) of the indicated clinical N stage Nx | 0 Participants | 6 Participants | 3 Participants | 3 Participants |
| Number of participants with the indicated FISH results Amplified | 115 Participants | 329 Participants | 109 Participants | 105 Participants |
| Number of participants with the indicated FISH results Not amplified | 1 Participants | 4 Participants | 1 Participants | 2 Participants |
| Number of participants with the indicated FISH results Not applicable | 38 Participants | 121 Participants | 41 Participants | 42 Participants |
| Number of participants with the indicated FISH results Not interpretable | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Number of participants with the indicated IHC results Equivocal: Score of 2+ | 9 Participants | 22 Participants | 8 Participants | 5 Participants |
| Number of participants with the indicated IHC results Negative: Score of 0-1+ | 0 Participants | 4 Participants | 3 Participants | 1 Participants |
| Number of participants with the indicated IHC results Non interpretable | 4 Participants | 9 Participants | 4 Participants | 1 Participants |
| Number of participants with the indicated IHC results Not applicable | 60 Participants | 174 Participants | 61 Participants | 53 Participants |
| Number of participants with the indicated IHC results Positive: Score of 3+ | 81 Participants | 246 Participants | 76 Participants | 89 Participants |
| Number of participants with tumor cells of the indicated histologic grade Differentiation cannot be assessed | 22 Participants | 65 Participants | 20 Participants | 23 Participants |
| Number of participants with tumor cells of the indicated histologic grade Missing | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Number of participants with tumor cells of the indicated histologic grade Moderately differentiated | 56 Participants | 172 Participants | 63 Participants | 53 Participants |
| Number of participants with tumor cells of the indicated histologic grade Poorly differentiated | 73 Participants | 205 Participants | 64 Participants | 68 Participants |
| Number of participants with tumor cells of the indicated histologic grade Well differentiated | 2 Participants | 12 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 13 Participants | 42 Participants | 15 Participants | 14 Participants |
| Race/Ethnicity, Customized Asian - Central/South | 7 Participants | 17 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian - East | 30 Participants | 89 Participants | 31 Participants | 28 Participants |
| Race/Ethnicity, Customized Asian - South East | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American/African Heritage | 0 Participants | 8 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 6 Participants | 14 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized White - Caucasian European Heritage | 97 Participants | 282 Participants | 92 Participants | 93 Participants |
| Sex: Female, Male Female | 154 Participants | 455 Participants | 152 Participants | 149 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 | 1 / 149 | 2 / 151 | 0 / 148 |
| other Total, other adverse events | 147 / 149 | 148 / 151 | 141 / 148 |
| serious Total, serious adverse events | 61 / 149 | 58 / 151 | 36 / 148 |
Outcome results
Primary
Number of Participants With Pathological Complete Response (pCR) at the Time of Surgery
Pathological complete response is defined as no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. Surgical breast and axillary node resection specimens were evaluated for pathologic tumor response according to National Surgical Adjuvant Breast and Bowel Project (NSABP) guidelines, which do not take into account the histological nodal status.
Time frame: Weeks 20 to 22
Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment, except for those who withdrew their consent to use any of their data (permitted by law in certain countries) prior to receiving any study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lapatinib 1500 mg | Number of Participants With Pathological Complete Response (pCR) at the Time of Surgery | 38 participants |
| Trastuzumab 2 mg/kg | Number of Participants With Pathological Complete Response (pCR) at the Time of Surgery | 44 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Number of Participants With Pathological Complete Response (pCR) at the Time of Surgery | 78 participants |
p-value: 0.341697.5% CI: [-17.6, 8.16]Binomial
p-value: 0.000197.5% CI: [9.08, 34.23]Binomial
Secondary
Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population)
The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis. Patients are considered in survival follow-up from randomisation until one of the following occurs: lost to follow-up, withdrawal of consent, end of follow-up due to completion of year 10 visit, termination of study follow-up, or death. For subjects with no death recorded in the database, time to death is censored.
Time frame: up to year 10
Population: For OS, the landmark population was the subset of the ITT population who were alive and were followed up for overall survival 30 weeks after randomization.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population) | Median survival follow-up - All subjects in the OS landmark analysis | 9.10 years |
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population) | Median survival follow-up - OS landmark analysis in the lapatinib + trastuzumab arm (n=67,72,139) | 9.14 years |
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population) | Median survival follow-up - OS landmark analysis in the lapatinib (n=30,109,139) | 8.31 years |
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population) | Median survival follow-up - OS landmark analysis in the trastuzumab arm (n=40,102,142) | 8.98 years |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population) | Median survival follow-up - OS landmark analysis in the trastuzumab arm (n=40,102,142) | 9.09 years |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population) | Median survival follow-up - All subjects in the OS landmark analysis | 9.09 years |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population) | Median survival follow-up - OS landmark analysis in the lapatinib (n=30,109,139) | 9.08 years |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population) | Median survival follow-up - OS landmark analysis in the lapatinib + trastuzumab arm (n=67,72,139) | 9.09 years |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population) | Median survival follow-up - OS landmark analysis in the trastuzumab arm (n=40,102,142) | 9.07 years |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population) | Median survival follow-up - OS landmark analysis in the lapatinib + trastuzumab arm (n=67,72,139) | 9.12 years |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population) | Median survival follow-up - OS landmark analysis in the lapatinib (n=30,109,139) | 9.07 years |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Median Clinical Follow-up (OS Landmark Population) | Median survival follow-up - All subjects in the OS landmark analysis | 9.09 years |
Comparison: Overall - All subjects in the OS landmark analysisp-value: 0.0004195% CI: [0.2, 0.63]Regression, Cox
Comparison: Subjects in the OS landmark analysis in the lapatinib + trastuzumab armp-value: 0.00295% CI: [0.07, 0.58]Regression, Cox
Comparison: Subjects in the OS landmark analysis in the lapatinib armp-value: 0.12595% CI: [0.12, 1.17]Regression, Cox
Comparison: Subjects in the OS landmark analysis in the trastuzumab armp-value: 0.05895% CI: [0.15, 1]Regression, Cox
Secondary
Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population)
The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis. Includes deaths due to any cause.
Time frame: up to year 10
Population: For OS, the landmark population was the subset of the ITT population who were alive and were followed up for overall survival 30 weeks after randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population) | All participants in the OS landmark analysis who died | 15 Number of Participants |
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population) | Participants in the OS landmark analysis in the lapatinib + trastuzumab arm who died (n=67,72,139) | 5 Number of Participants |
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population) | Participants in the OS landmark analysis in the lapatinib arm who died (n=30,109,139) | 4 Number of Participants |
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population) | Participants in the OS landmark analysis in the trastuzumab arm who died (n=40,102,142) | 6 Number of Participants |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population) | Participants in the OS landmark analysis in the trastuzumab arm who died (n=40,102,142) | 25 Number of Participants |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population) | All participants in the OS landmark analysis who died | 70 Number of Participants |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population) | Participants in the OS landmark analysis in the lapatinib arm who died (n=30,109,139) | 26 Number of Participants |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population) | Participants in the OS landmark analysis in the lapatinib + trastuzumab arm who died (n=67,72,139) | 19 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population) | Participants in the OS landmark analysis in the trastuzumab arm who died (n=40,102,142) | 31 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population) | Participants in the OS landmark analysis in the lapatinib + trastuzumab arm who died (n=67,72,139) | 24 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population) | Participants in the OS landmark analysis in the lapatinib arm who died (n=30,109,139) | 30 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and and Overall Survival (OS) - Number of Participants Who Died (OS Landmark Population) | All participants in the OS landmark analysis who died | 85 Number of Participants |
Secondary
Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population)
The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis. Clinical follow-up is the period during which the patient is monitored such that all recurrence or second primary malignancy (SPM) or contralateral breast cancer (CBC) events would be reported. Patients are considered in clinical follow-up from randomisation until one of the following occurs: lost to follow-up, withdrawal of consent, end of follow-up due to completion of year 10 visit, termination of study follow-up, or death.
Time frame: up to year 10
Population: For EFS, the landmark population was the subset of the ITT population who have not had an EFS event within 30 weeks after randomization and were still in clinical follow-up.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population) | Median clinical follow-up - all subjects in the EFS landmark analysis | 9.05 years |
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population) | Median clinical follow-up- EFS landmark analysis - lapatinib + trastuzumab arm (n=67,71,138) | 9.13 years |
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population) | Median clinical follow-up - subjects in the EFS landmark analysis - lapatinib arm (n=30,104,134) | 8.08 years |
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population) | Median clinical follow-up - subjects in the EFS landmark analysis - trastuzumab arm (n=39,99,138) | 8.98 years |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population) | Median clinical follow-up - subjects in the EFS landmark analysis - trastuzumab arm (n=39,99,138) | 9.12 years |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population) | Median clinical follow-up - all subjects in the EFS landmark analysis | 9.11 years |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population) | Median clinical follow-up - subjects in the EFS landmark analysis - lapatinib arm (n=30,104,134) | 9.09 years |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population) | Median clinical follow-up- EFS landmark analysis - lapatinib + trastuzumab arm (n=67,71,138) | 9.10 years |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population) | Median clinical follow-up - subjects in the EFS landmark analysis - trastuzumab arm (n=39,99,138) | 9.11 years |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population) | Median clinical follow-up- EFS landmark analysis - lapatinib + trastuzumab arm (n=67,71,138) | 9.12 years |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population) | Median clinical follow-up - subjects in the EFS landmark analysis - lapatinib arm (n=30,104,134) | 9.05 years |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Median Clinical Follow-up (EFS Landmark Population) | Median clinical follow-up - all subjects in the EFS landmark analysis | 9.09 years |
Comparison: Overall - All subjects in the EFS landmark analysisp-value: 0.0007995% CI: [0.31, 0.73]Regression, Cox
Comparison: Subjects in the EFS landmark analysis in the lapatinib + trastuzumab armp-value: 0.00495% CI: [0.16, 0.71]Regression, Cox
Comparison: Subjects in the EFS landmark analysis in the lapatinib armp-value: 0.13495% CI: [0.21, 1.16]Regression, Cox
Comparison: Subjects in the EFS landmark analysis in the trastuzumab armp-value: 0.16395% CI: [0.28, 1.2]Regression, Cox
Secondary
Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population)
The landmark date is 30 weeks after a subject's randomization. Subjects with missing pCR status were not included in the landmark analysis. For patients who had breast cancer surgery, EFS events are post-surgery breast cancer relapse, second primary malignancy or death without recurrence. For patients who do not undergo breast cancer surgery, EFS events are death during clinical follow-up or non-completion of any neo-adjuvant investigational product due to disease progression or second primary malignancy or contralateral breast cancer.
Time frame: up to year 10
Population: For EFS, the landmark population was the subset of the ITT population who have not had an EFS event within 30 weeks after randomization and were still in clinical follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population) | All subjects in the EFS landmark analysis with EFS events | 29 Number of participants |
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population) | Subjects in the EFS landmark analysis - lapatinib + trastuzumab arm with EFS events (n=67,71,138) | 11 Number of participants |
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population) | Subjects in the EFS landmark analysis in the lapatinib arm with EFS events (n=30,104,134) | 7 Number of participants |
| Lapatinib 1500 mg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population) | Subjects in the EFS landmark analysis in the trastuzumab arm with EFS events (n=39,99,138) | 11 Number of participants |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population) | Subjects in the EFS landmark analysis in the trastuzumab arm with EFS events (n=39,99,138) | 34 Number of participants |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population) | All subjects in the EFS landmark analysis with EFS events | 98 Number of participants |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population) | Subjects in the EFS landmark analysis in the lapatinib arm with EFS events (n=30,104,134) | 36 Number of participants |
| Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population) | Subjects in the EFS landmark analysis - lapatinib + trastuzumab arm with EFS events (n=67,71,138) | 28 Number of participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population) | Subjects in the EFS landmark analysis in the trastuzumab arm with EFS events (n=39,99,138) | 45 Number of participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population) | Subjects in the EFS landmark analysis - lapatinib + trastuzumab arm with EFS events (n=67,71,138) | 39 Number of participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population) | Subjects in the EFS landmark analysis in the lapatinib arm with EFS events (n=30,104,134) | 43 Number of participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Assess Associations Between Locoregional Pathological Complete Response (pCR) and Event-free Survival (EFS) - Number of Participants With EFS Events (EFS Landmark Population) | All subjects in the EFS landmark analysis with EFS events | 127 Number of participants |
Secondary
Event-free Survival (EFS) - Events and Censoring
Event free survival (EFS) is defined as the time from randomization to first EFS event. For subjects who had breast cancer surgery, EFS events were post-surgery breast cancer relapse, second primary malignancy or death without recurrence. For subjects who did not have breast cancer surgery, EFS events were death during clinical follow-up or non-completion of any neoadjuvant investigational product due to disease progression.
Time frame: From randomization up to approximately year 10
Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment, except for those who withdrew their consent to use any of their data (permitted by law in certain countries) prior to receiving any study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib 1500 mg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ended - total | 103 Number of Participants |
| Lapatinib 1500 mg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Other | 6 Number of Participants |
| Lapatinib 1500 mg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ended - Lost to follow-up | 17 Number of Participants |
| Lapatinib 1500 mg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored -Clinical follow-up ended - Completed study follow-up | 61 Number of Participants |
| Lapatinib 1500 mg | Event-free Survival (EFS) - Events and Censoring | Number of subjects with EFS events | 43 Number of Participants |
| Lapatinib 1500 mg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ended - Withdrew | 22 Number of Participants |
| Lapatinib 1500 mg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ongoing | 0 Number of Participants |
| Lapatinib 1500 mg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - total | 109 Number of Participants |
| Lapatinib 1500 mg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ended - Withdrew (but consent for survival f/u) | 3 Number of Participants |
| Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored -Clinical follow-up ended - Completed study follow-up | 49 Number of Participants |
| Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects with EFS events | 47 Number of Participants |
| Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - total | 107 Number of Participants |
| Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ongoing | 0 Number of Participants |
| Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ended - total | 105 Number of Participants |
| Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ended - Lost to follow-up | 20 Number of Participants |
| Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ended - Withdrew (but consent for survival f/u) | 6 Number of Participants |
| Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ended - Withdrew | 30 Number of Participants |
| Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Other | 2 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ongoing | 0 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects with EFS events | 47 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ended - Withdrew (but consent for survival f/u) | 4 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - total | 102 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Other | 3 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored -Clinical follow-up ended - Completed study follow-up | 58 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ended - total | 99 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ended - Withdrew | 27 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Events and Censoring | Number of subjects censored - Clinical follow-up ended - Lost to follow-up | 10 Number of Participants |
p-value: 0.54895% CI: [0.57, 1.34]Regression, Cox
p-value: 0.98195% CI: [0.66, 1.52]Regression, Cox
Secondary
Event-free Survival (EFS) - Median Clinical Follow-up
Event free survival (EFS) is defined as the time from randomization to first EFS event. For subjects who had breast cancer surgery, EFS events were post-surgery breast cancer relapse, second primary malignancy or death without recurrence. For subjects who did not have breast cancer surgery, EFS events were death during clinical follow-up or non-completion of any neoadjuvant investigational product due to disease progression.
Time frame: From randomization up to approximately year 10
Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment, except for those who withdrew their consent to use any of their data (permitted by law in certain countries) prior to receiving any study medication
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lapatinib 1500 mg | Event-free Survival (EFS) - Median Clinical Follow-up | 9.69 years |
| Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Median Clinical Follow-up | 9.60 years |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Event-free Survival (EFS) - Median Clinical Follow-up | 9.66 years |
Secondary
Mean Change From Baseline in Tumor Size at Week 6 and at Surgery
Mean change from baseline in tumor in tumor size. Change from baseline in tumor size was defined as tumor size at Week 6/ surgery (Weeks 20 to 22) minus tumor size at baseline. The difference in treatment arms was estimated for Lapatinib 1500 mg versus Trastuzumab 2 mg/kg and for Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg versus Trastuzumab 2 mg/kg.
Time frame: Week 6 and surgery (Weeks 20 to 22)
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lapatinib 1500 mg | Mean Change From Baseline in Tumor Size at Week 6 and at Surgery | Week 6 | -20.45 millimeters | Standard Deviation 18.43 |
| Lapatinib 1500 mg | Mean Change From Baseline in Tumor Size at Week 6 and at Surgery | Surgery (Weeks 20 to 22) | -41.01 millimeters | Standard Deviation 23.81 |
| Trastuzumab 2 mg/kg | Mean Change From Baseline in Tumor Size at Week 6 and at Surgery | Week 6 | -13.42 millimeters | Standard Deviation 16.44 |
| Trastuzumab 2 mg/kg | Mean Change From Baseline in Tumor Size at Week 6 and at Surgery | Surgery (Weeks 20 to 22) | -35.47 millimeters | Standard Deviation 22.95 |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Mean Change From Baseline in Tumor Size at Week 6 and at Surgery | Week 6 | -25.77 millimeters | Standard Deviation 19.91 |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Mean Change From Baseline in Tumor Size at Week 6 and at Surgery | Surgery (Weeks 20 to 22) | -43.59 millimeters | Standard Deviation 26.88 |
Secondary
Metabolic Response Rate Determined by Positron Emission Tomography/Computed Tomography (PET/CT)
Metabolic Response Rate determined by Positron Emission Tomography/Computed Tomography (PET/CT)
Time frame: Week 2 and Week 6
Population: Translational Data Set. Note that evaluable samples were not available for all participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib 1500 mg | Metabolic Response Rate Determined by Positron Emission Tomography/Computed Tomography (PET/CT) | Metabolic Response Rate (%) Determined by PET/CT at week 2 | 66.7 Percentage of participants |
| Lapatinib 1500 mg | Metabolic Response Rate Determined by Positron Emission Tomography/Computed Tomography (PET/CT) | Metabolic Response Rate (%) Determined by PET/CT at week 6 | 60.9 Percentage of participants |
| Trastuzumab 2 mg/kg | Metabolic Response Rate Determined by Positron Emission Tomography/Computed Tomography (PET/CT) | Metabolic Response Rate (%) Determined by PET/CT at week 2 | 56.5 Percentage of participants |
| Trastuzumab 2 mg/kg | Metabolic Response Rate Determined by Positron Emission Tomography/Computed Tomography (PET/CT) | Metabolic Response Rate (%) Determined by PET/CT at week 6 | 43.5 Percentage of participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Metabolic Response Rate Determined by Positron Emission Tomography/Computed Tomography (PET/CT) | Metabolic Response Rate (%) Determined by PET/CT at week 2 | 95.0 Percentage of participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Metabolic Response Rate Determined by Positron Emission Tomography/Computed Tomography (PET/CT) | Metabolic Response Rate (%) Determined by PET/CT at week 6 | 78.9 Percentage of participants |
Secondary
Number of Participants Starting Paclitaxel Before Completing 6 Weeks of Treatment With Either Lapatinib or Trastuzumab
Participants with progressive disease at 4 week assessment that were permitted to commence treatment with paclitaxel.
Time frame: Week 6
Population: ITT Population. Participants who did not start any treatment were excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lapatinib 1500 mg | Number of Participants Starting Paclitaxel Before Completing 6 Weeks of Treatment With Either Lapatinib or Trastuzumab | 8 participants |
| Trastuzumab 2 mg/kg | Number of Participants Starting Paclitaxel Before Completing 6 Weeks of Treatment With Either Lapatinib or Trastuzumab | 12 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Number of Participants Starting Paclitaxel Before Completing 6 Weeks of Treatment With Either Lapatinib or Trastuzumab | 6 participants |
Secondary
Number of Participants With Actual Indicated Surgery
Participants were assessed for the type of surgery they underwent for breast cancer. Non-conservative surgery is defined as a radical or modified radical mastectomy. Conservative surgery is comprised of a lumpectomy, a quadrantectomy/segmentectomy, or a partial mastectomy. Participants who were not assessed as being candidates for non-conservative or conservative surgery were classified as non-operable.
Time frame: At surgery (Weeks 20 to 22)
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib 1500 mg | Number of Participants With Actual Indicated Surgery | Non-conservative | 77 participants |
| Lapatinib 1500 mg | Number of Participants With Actual Indicated Surgery | Conservative | 66 participants |
| Lapatinib 1500 mg | Number of Participants With Actual Indicated Surgery | Non-operable | 11 participants |
| Trastuzumab 2 mg/kg | Number of Participants With Actual Indicated Surgery | Non-conservative | 85 participants |
| Trastuzumab 2 mg/kg | Number of Participants With Actual Indicated Surgery | Conservative | 58 participants |
| Trastuzumab 2 mg/kg | Number of Participants With Actual Indicated Surgery | Non-operable | 6 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Number of Participants With Actual Indicated Surgery | Conservative | 63 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Number of Participants With Actual Indicated Surgery | Non-operable | 9 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Number of Participants With Actual Indicated Surgery | Non-conservative | 80 participants |
Secondary
Number of Participants With Negative Lymph Nodes at the Time of Surgery
Participants were assessed for node-negative lymph nodes at the time of surgery. As per the pathological TNM (Tumor, Node, Metastases) classification (pTNM) of malignant tumors: pN, absence or presence and extent of regional lymph node metastasis. Node-negative (pN0) participants had no regional lymph node metastasis. Although not assessed in this measure, pT is the extent of primary tumor, and pM is the absence or presence of distant metastasis.
Time frame: Time of surgery (Weeks 20 to 22)
Population: ITT Population. Participants with a lymph node status of pNX (i.e., regional lymph nodes cannot be assessed) were omitted from the analysis of node-negative participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lapatinib 1500 mg | Number of Participants With Negative Lymph Nodes at the Time of Surgery | 72 participants |
| Trastuzumab 2 mg/kg | Number of Participants With Negative Lymph Nodes at the Time of Surgery | 82 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Number of Participants With Negative Lymph Nodes at the Time of Surgery | 100 participants |
Secondary
Number of Participants With Overall Response at Week 6
The number of participants with overall response (complete response and/or partial response) was evaluated using World Health Organization (WHO) criteria by clinical examination and by mammography and breast echography with bi-dimensional measurements at Week 6. As per WHO criteria: complete response is defined as the disappearance of all lesions; partial response is defined as a greater than 50% decrease in the sum of products of the greatest length and width of the largest lesion; progressive disease is defined as a greater than 25% increase in the sum of products of all measurable lesions.
Time frame: Week 6
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib 1500 mg | Number of Participants With Overall Response at Week 6 | Not Evaluated | 7 participants |
| Lapatinib 1500 mg | Number of Participants With Overall Response at Week 6 | Progressive Disease | 5 participants |
| Lapatinib 1500 mg | Number of Participants With Overall Response at Week 6 | Overall Response | 81 participants |
| Lapatinib 1500 mg | Number of Participants With Overall Response at Week 6 | No Change | 57 participants |
| Lapatinib 1500 mg | Number of Participants With Overall Response at Week 6 | Missing Data | 4 participants |
| Trastuzumab 2 mg/kg | Number of Participants With Overall Response at Week 6 | Progressive Disease | 11 participants |
| Trastuzumab 2 mg/kg | Number of Participants With Overall Response at Week 6 | Overall Response | 45 participants |
| Trastuzumab 2 mg/kg | Number of Participants With Overall Response at Week 6 | No Change | 81 participants |
| Trastuzumab 2 mg/kg | Number of Participants With Overall Response at Week 6 | Not Evaluated | 9 participants |
| Trastuzumab 2 mg/kg | Number of Participants With Overall Response at Week 6 | Missing Data | 3 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Number of Participants With Overall Response at Week 6 | Missing Data | 3 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Number of Participants With Overall Response at Week 6 | Not Evaluated | 12 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Number of Participants With Overall Response at Week 6 | Overall Response | 102 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Number of Participants With Overall Response at Week 6 | Progressive Disease | 2 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Number of Participants With Overall Response at Week 6 | No Change | 33 participants |
Secondary
Overall Response at the Time of Surgery
The number of participants with overall response (complete response and/or partial response) was evaluated using WHO criteria by clinical examination and mammography and breast echography with bi-dimensional measurements at the time of surgery (Weeks 20 to 22). As per WHO criteria: complete response is defined as the disappearance of all lesions; partial response is defined as a greater than 50% decrease in the sum of products of the greatest length and width of the largest lesion; progressive disease is defined as a greater than 25% increase in the sum of products of all measurable lesions.
Time frame: Time of surgery (Weeks 20 to 22)
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib 1500 mg | Overall Response at the Time of Surgery | Not Evaluated | 19 participants |
| Lapatinib 1500 mg | Overall Response at the Time of Surgery | Progressive Disease | 0 participants |
| Lapatinib 1500 mg | Overall Response at the Time of Surgery | Overall Response | 114 participants |
| Lapatinib 1500 mg | Overall Response at the Time of Surgery | No Change | 8 participants |
| Lapatinib 1500 mg | Overall Response at the Time of Surgery | Missing Data | 13 participants |
| Trastuzumab 2 mg/kg | Overall Response at the Time of Surgery | Progressive Disease | 2 participants |
| Trastuzumab 2 mg/kg | Overall Response at the Time of Surgery | Overall Response | 105 participants |
| Trastuzumab 2 mg/kg | Overall Response at the Time of Surgery | No Change | 16 participants |
| Trastuzumab 2 mg/kg | Overall Response at the Time of Surgery | Not Evaluated | 20 participants |
| Trastuzumab 2 mg/kg | Overall Response at the Time of Surgery | Missing Data | 6 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Response at the Time of Surgery | Missing Data | 8 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Response at the Time of Surgery | Not Evaluated | 14 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Response at the Time of Surgery | Overall Response | 122 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Response at the Time of Surgery | Progressive Disease | 1 participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Response at the Time of Surgery | No Change | 7 participants |
Secondary
Overall Survival (OS) - Deaths and Censoring
Overall survival is defined as the period from randomization until death (from any cause). OS was assessed annually for up to 10 years after the randomization of the last participant into the study.
Time frame: From randomization up to approximately year 10
Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment, except for those who withdrew their consent to use any of their data (permitted by law in certain countries) prior to receiving any study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib 1500 mg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Other | 6 Number of Participants |
| Lapatinib 1500 mg | Overall Survival (OS) - Deaths and Censoring | Number of deaths due to any cause | 26 Number of Participants |
| Lapatinib 1500 mg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Survival follow-up ended - total | 120 Number of Participants |
| Lapatinib 1500 mg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Survival follow-up ended - Withdrew | 24 Number of Participants |
| Lapatinib 1500 mg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - total | 126 Number of Participants |
| Lapatinib 1500 mg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored -Survival follow-up ended - Completed study follow-up | 74 Number of Participants |
| Lapatinib 1500 mg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Survival follow-up ongoing | 0 Number of Participants |
| Lapatinib 1500 mg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Survival follow-up ended - Lost to follow-up | 22 Number of Participants |
| Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - total | 123 Number of Participants |
| Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Survival follow-up ended - Lost to follow-up | 27 Number of Participants |
| Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of deaths due to any cause | 31 Number of Participants |
| Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Survival follow-up ended - Withdrew | 35 Number of Participants |
| Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Other | 2 Number of Participants |
| Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Survival follow-up ongoing | 0 Number of Participants |
| Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Survival follow-up ended - total | 121 Number of Participants |
| Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored -Survival follow-up ended - Completed study follow-up | 59 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Other | 3 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of deaths due to any cause | 32 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - total | 117 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Survival follow-up ongoing | 0 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Survival follow-up ended - total | 114 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored -Survival follow-up ended - Completed study follow-up | 62 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Survival follow-up ended - Lost to follow-up | 18 Number of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Survival (OS) - Deaths and Censoring | Number of subjects censored - Survival follow-up ended - Withdrew | 34 Number of Participants |
p-value: 0.37995% CI: [0.46, 1.34]Regression, Cox
p-value: 0.8895% CI: [0.58, 1.6]Regression, Cox
Secondary
Overall Survival (OS) - Median Survival Follow-up
Overall survival is defined as the period from randomization until death (from any cause). OS was assessed annually for up to 10 years after the randomization of the last participant into the study.
Time frame: From randomization up to approximately year 10
Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment, except for those who withdrew their consent to use any of their data (permitted by law in certain countries) prior to receiving any study medication
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lapatinib 1500 mg | Overall Survival (OS) - Median Survival Follow-up | 9.70 years |
| Trastuzumab 2 mg/kg | Overall Survival (OS) - Median Survival Follow-up | 9.62 years |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Overall Survival (OS) - Median Survival Follow-up | 9.64 years |
Secondary
Percentage of Participants With Circulating Tumor Cells (CTC) in the Bloodstream
Circulating tumor cells (CTCs) are cells that have detached from a primary tumor and circulate in the bloodstream. In the adjuvant phase, after surgery all participants received 3 courses of adjuvant 5-fluorouracil, epirubicin and cyclophosphamide, followed by lapatinib 1500 mg or trastuzumab 2 mg/kg or lapatinib 1000/750 mg plus trastuzumab 2 mg/kg given prior to surgery in the neoadjuvant setting for an additional 34 weeks.
Time frame: Measurement performed at one or more of the time points: baseline, week 2 or week 18
Population: Translational Data Set. Note that evaluable samples were not available for all participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lapatinib 1500 mg | Percentage of Participants With Circulating Tumor Cells (CTC) in the Bloodstream | 21 Percentage of Participants |
| Trastuzumab 2 mg/kg | Percentage of Participants With Circulating Tumor Cells (CTC) in the Bloodstream | 17 Percentage of Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Percentage of Participants With Circulating Tumor Cells (CTC) in the Bloodstream | 25 Percentage of Participants |
Secondary
Percentage of Participants With the Indicated Biomarker Expression - PIK3CA.
Biomarker levels of phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) were assessed in participants at baseline.
Time frame: Baseline
Population: Translational Data Set. Note that evaluable samples were not available for all participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lapatinib 1500 mg | Percentage of Participants With the Indicated Biomarker Expression - PIK3CA. | 23 Percentage of participants |
| Trastuzumab 2 mg/kg | Percentage of Participants With the Indicated Biomarker Expression - PIK3CA. | 19 Percentage of participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Percentage of Participants With the Indicated Biomarker Expression - PIK3CA. | 25 Percentage of participants |
Secondary
Percentage of Participants With the Indicated Biomarker Expression - PTEN.
Biomarker levels of phosphate and tensin homolog deleted from chromosome 10 (PTEN) were assessed in participants at baseline.
Time frame: Baseline
Population: Translational Data Set. Note that evaluable samples were not available for all participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib 1500 mg | Percentage of Participants With the Indicated Biomarker Expression - PTEN. | Biomarker: PTEN by Cell Signalling Technology - PTEN Normal (%) | 74 Percentage of participants |
| Lapatinib 1500 mg | Percentage of Participants With the Indicated Biomarker Expression - PTEN. | Biomarker: PTEN by Cell Signalling Technology - PTEN Loss (%) | 26 Percentage of participants |
| Trastuzumab 2 mg/kg | Percentage of Participants With the Indicated Biomarker Expression - PTEN. | Biomarker: PTEN by Cell Signalling Technology - PTEN Normal (%) | 70 Percentage of participants |
| Trastuzumab 2 mg/kg | Percentage of Participants With the Indicated Biomarker Expression - PTEN. | Biomarker: PTEN by Cell Signalling Technology - PTEN Loss (%) | 30 Percentage of participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Percentage of Participants With the Indicated Biomarker Expression - PTEN. | Biomarker: PTEN by Cell Signalling Technology - PTEN Normal (%) | 75 Percentage of participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Percentage of Participants With the Indicated Biomarker Expression - PTEN. | Biomarker: PTEN by Cell Signalling Technology - PTEN Loss (%) | 25 Percentage of participants |
Secondary
Ratio (95% CI) of Geometric Means in p95HER2 Expression in HR Positive Patients With pCR vs no pCR
Ratio (95% CI) of geometric means in p95 human epidermal growth factor receptor (p95HER2) expression in hormone-receptor (HR) positive patients with pathological complete response (pCR) vs no pCR
Time frame: Baseline
Population: Translational Data Set. Note that evaluable samples were not available for all participants.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Lapatinib 1500 mg | Ratio (95% CI) of Geometric Means in p95HER2 Expression in HR Positive Patients With pCR vs no pCR | 1.0 Ratio |
| Trastuzumab 2 mg/kg | Ratio (95% CI) of Geometric Means in p95HER2 Expression in HR Positive Patients With pCR vs no pCR | 1.6 Ratio |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | Ratio (95% CI) of Geometric Means in p95HER2 Expression in HR Positive Patients With pCR vs no pCR | 2.1 Ratio |
Secondary
To Assess Safety Via a Comparison of the Three Treatment Arms - to Measure On-treatment Primary Cardiac Endpoints
Time frame: Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of 31 weeks.
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lapatinib 1500 mg | To Assess Safety Via a Comparison of the Three Treatment Arms - to Measure On-treatment Primary Cardiac Endpoints | 2 Participants |
| Trastuzumab 2 mg/kg | To Assess Safety Via a Comparison of the Three Treatment Arms - to Measure On-treatment Primary Cardiac Endpoints | 0 Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | To Assess Safety Via a Comparison of the Three Treatment Arms - to Measure On-treatment Primary Cardiac Endpoints | 1 Participants |
Post Hoc
All Collected Deaths
On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, which was approximately 31 weeks. Deaths post treatment survival follow up were collected after the on treatment period, up to 10 years.
Time frame: on-treatment: up to week 31; post-treatment: up to year 10
Population: Safety population (for on-treatment deaths) and ITT (for total deaths)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib 1500 mg | All Collected Deaths | Total Deaths | 31 Participants |
| Lapatinib 1500 mg | All Collected Deaths | On-Treatment Deaths (n=151,148,149) | 2 Participants |
| Trastuzumab 2 mg/kg | All Collected Deaths | Total Deaths | 32 Participants |
| Trastuzumab 2 mg/kg | All Collected Deaths | On-Treatment Deaths (n=151,148,149) | 0 Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | All Collected Deaths | Total Deaths | 26 Participants |
| Lapatinib 1000/750 mg + Trastuzumab 2 mg/kg | All Collected Deaths | On-Treatment Deaths (n=151,148,149) | 1 Participants |