Breast Cancer
Conditions
Brief summary
This 2-arm, randomized, open-label study will evaluate the efficacy and safety of trastuzumab emtansine versus trastuzumab as adjuvant therapy in patients with HER2-positive breast cancer who have residual tumor present in the breast or axillary lymph nodes following preoperative therapy. Eligible patients will be randomized to receive either trastuzumab emtansine 3.6 mg/kg or trastuzumab 6 mg/kg intravenously every 3 weeks for 14 cycles. Radiotherapy and/or hormone therapy will be given in addition if indicated.
Interventions
DRUGtrastuzumab
6 mg/kg intravenously every 3 weeks, 14 cycles
DRUGtrastuzumab emtansine
3.6 mg/kg intravenously every 3 weeks, 14 cycles
Sponsors
NSABP Foundation Inc
GBG Forschungs GmbH
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patient, \>/= 18 years of age * HER2-positive breast cancer * Histologically confirmed invasive breast carcinoma * Clinical stage T1-4/N0-3/M0 at presentation (patients with T1a/bN0 tumors will not be eligible) * Completion of preoperative systemic chemotherapy and HER2-directed treatment consisting of at least 6 cycles of chemotherapy with a total duration of at least 16 weeks, including at least 9 weeks of trastuzumab and at least 9 weeks of taxane-based therapy * Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes as specified in protocol * Pathological evidence of residual invasive carcinoma in the breast or axillary lymph nodes following completion of preoperative therapy * An interval of no more than 12 weeks between the date of surgery and the date of randomization * Known hormone-receptor status * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Adequate hematologic, renal and liver function * Screening Left ventricular ejection fraction (LVEF) \>/= 50% on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no decrease in LVEF by more than 15% absolute points from the pre-chemotherapy LVEF. Or, if pre-chemotherapy LVEF was not assessed, the screening LVEF must be \>/= 55% after completion of neoadjuvant chemotherapy. * For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 7 months after the last dose of study drug * Documentation of hepatitis B virus and hepatitis C virus serology is required
Exclusion criteria
* Stage IV (metastatic) breast cancer * History of any prior (ipsi- or contralateral breast cancer except lobular carcinoma in situ * Evidence of clinically evident gross residual or recurrent disease following preoperative therapy and surgery * Progressive disease during preoperative systemic therapy * Treatment with any anti-cancer investigational drug within 28 days prior to commencing study treatment * History of other malignancy within the last 5 years except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other non-breast malignancies with a similar outcome to those mentioned above * Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons * Current NCI CTCAE (Version 4.0) Grade \>/= 2 peripheral neuropathy * History of exposure to the following cumulative doses of anthracyclines: Doxorubicin \> 240 mg/m2; Epirubicin or Liposomal Doxorubicin-Hydrochloride (Myocet®) \> 480 mg/m2; For other anthracyclines, exposure equivalent to doxorubicin \> 240 mg/m2 * Cardiopulmonary dysfunction as defined by protocol * Prior treatment with trastuzumab emtansine * Current severe, uncontrolled systemic disease * Pregnant or lactating women * Any known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitis * Concurrent serious uncontrolled infections requiring treatment or known infection with HIV * History of intolerance, including Grade 3 to 4 infusion reaction or hypersensitivity to trastuzumab or murine proteins or any components of the product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Disease-free Survival (IDFS) Rate at 3 Years | At Year 3 | IDFS event was defined as the first occurrence of any one of the following events: ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site-other than the 2 above-mentioned sites - that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; death attributable to any cause including breast cancer, non-breast cancer or unknown cause . 3-year IDFS rate in ITT population was estimated using Kaplan Meier (KM) method and the percentage of participants who were event-free 3 years after randomization was estimated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IDFS Including Second Primary Non-breast Cancer (SPNBC) Rate at 3 Years | At Year 3 | IDFS including SPNBC was defined the same way as IDFS but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and carcinoma in situ \[CIS\] of any site). IDFS event was defined as outlined in the description for IDFS rate outcome measure (OM) number 1. 3-year IDFS including SPNBC rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 3 years after randomization was estimated. |
| IDFS Including SPNBC Rate at 7 Years | At Year 7 | IDFS including SPNBC was defined the same way as IDFS but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and CIS of any site). IDFS event was defined as outlined in the description for IDFS rate OM number 1. 7-year IDFS including SPNBC rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 7 years after randomization was estimated. |
| IDFS Including SPNBC Rate at 8 Years | At Year 8 | IDFS including SPNBC was defined the same way as IDFS but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and CIS of any site). IDFS event was defined as outlined in the description for IDFS rate OM number 1. 8-year IDFS including SPNBC rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 8 years after randomization was estimated. |
| Disease-free Survival (DFS) Rate at 3 Years | At Year 3 | DFS was defined as the time between randomization and the date of the first occurrence of an IDFS event including SPNBC event or contralateral or ipsilateral ductal carcinoma in situ (DCIS). IDFS event was defined as outlined in the description for IDFS rate OM number 1. 3-year DFS rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 3 years after randomization was estimated. |
| DFS Rate at 7 Years | At Year 7 | DFS was defined as the time between randomization and the date of the first occurrence of an IDFS event including SPNBC event or contralateral or ipsilateral DCIS. IDFS event was defined as outlined in the description for IDFS rate OM number 1. 7-year DFS rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 7 years after randomization was estimated. |
| DFS Rate at 8 Years | At Year 8 | DFS was defined as the time between randomization and the date of the first occurrence of an IDFS event including SPNBC event or contralateral or ipsilateral DCIS. IDFS event was defined as outlined in the description for IDFS rate OM number 1. 8-year DFS rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 8 years after randomization was estimated. |
| Overall Survival (OS) Rate at 5 Years | At Year 5 | OS was defined as the time from randomization to death due to any cause. 5-year OS event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 5 years after randomization was estimated. |
| OS Rate at 7 Years | At Year 7 | OS was defined as the time from randomization to death due to any cause. 7-year OS event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 7 years after randomization was estimated. |
| OS Rate at 8 Years | At Year 8 | OS was defined as the time from randomization to death due to any cause. 8-year OS event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 8 years after randomization was estimated. |
| Distant Recurrence-free Interval (DRFI) Rate at 3 Years | At Year 3 | DRFI was defined as the time between randomization and the date of distant breast cancer recurrence. 3-year DRFI event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 3 years after randomization was estimated. |
| DRFI Rate at 7 Years | At Year 7 | DRFI was defined as the time between randomization and the date of distant breast cancer recurrence. 7-year DRFI event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 7 years after randomization was estimated. |
| DRFI Rate at 8 Years | At Year 8 | DRFI was defined as the time between randomization and the date of distant breast cancer recurrence. 8-year DRFI event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 8 years after randomization was estimated. |
| Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From signing of informed consent till end of follow up (up to approximately 131 months) | AE=any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. AE can therefore be any unfavorable & unintended sign (including abnormal laboratory finding), symptom/disease temporally associated with use of a medicinal product, whether or not considered related to medicinal product. SAE=any AE that met any given criteria: fatal (i.e. AE causes/leads to death); life-threatening (i.e. AE, in view of investigator, placed the participant at immediate risk of death); required/prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity (i.e. AE results in substantial disruption of participant's ability to conduct normal life functions); congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug; significant medical event in investigator's judgment. Percentages have been rounded off. |
| Number of Participants With Positive Anti-drug Antibodies (ADAs) to Trastuzumab Emtansine | Baseline (Day1 of Cycle1) and Post Baseline (Day 1 of Cycle 4 up to 3-4 months after last dose of the drug [up to approximately 13.6 months]) | ADA-positive participants after drug administration were determined for participants exposed to trastuzumab emtansine. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the baseline titer result. The total number of participants who developed ADAs to trastuzumab emtansine was determined by summing the ADA-positive participants across all timepoints. |
| Number of Participants With Positive ADAs to Trastuzumab | Baseline (Day1 of Cycle1) and Post Baseline (Day 1 of Cycle 4 up to 3-4 months after last dose of the drug [up to approximately 13.6 months]) | ADA-positive participants after drug administration were determined for participants exposed to trastuzumab. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 t.u. greater than the baseline titer result. The total number of participants who developed ADAs to trastuzumab was determined by summing the ADA-positive participants across all timepoints. |
| Percentage of Participants With Cardiac Events as Adjudicated by the Cardiac Review Committee | Up to approximately 126 months | Cardiac events were defined as death from cardiac cause or severe congestive heart failure (New York Heart Association \[NYHA\] Class III or IV) with a decrease in left ventricular ejection fraction (LVEF) of 10 percentage points or more from baseline to an LVEF of \< 50%. Other cardiac-related events (e.g., any symptomatic congestive heart failure \[CHF\] associated with a 10% drop in LVEF to \< 50%; asymptomatic declines in LVEF requiring dose delay) were summarized as adjudicated by the Cardiac Review Committee. Percentages have been rounded off. |
| Percentage of Participants With Hepatotoxicity Events as Adjudicated by the Hepatic Review Committee | Up to approximately 64 months | Hepatotoxicity events were summarized by treatment arm. Hepatotoxicity events were assessed using liver function laboratory test (LFT) results which included the analysis of baseline and post-baseline levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBILI), and alkaline phosphatase (ALK). Hepatic events, as adjudicated by the Hepatic Review Committee, are summarized. Percentages have been rounded off. |
| Number of Participants Who Discontinued Treatment Due to AEs | Up to approximately 9.6 months | An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants were treated for up to 14 cycles (1 cycle = 21 days). |
| Number of Participants With AEs and SAEs Leading to Death | From signing of informed consent till end of follow up (up to approximately 131 months) | An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was any AE that met any of the following criteria: fatal (i.e., the AE actually causes or leads to death); life-threatening (i.e., the AE, in the view of the investigator, placed the participant at immediate risk of death); required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity (i.e., the AE results in substantial disruption of the participant's ability to conduct normal life functions); congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug; significant medical event in the investigator's judgment. |
| Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline, Cycles 5 &11, Follow-up (FU) Month 6, FU Month 12 (1 cycle = 21 days) | The EORTC QLQ-C30 consists of 30 questions which assess five functional domains (physical, role, cognitive, emotional, and social), a global health status/quality of life (GHS/QoL) scale, three symptom scales (fatigue, pain, nausea, and vomiting), five single items (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea), and a perceived financial impact of the disease item. Most questions used a 4-point scale (1= Not at all to 4 = Very much; 2 questions used a 7-point scale \[1 = very poor to 7 = Excellent\]). Obtained scores are linearly transformed to a score range of 0-100, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms. A positive change from baseline indicates improvement. |
| Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline, Cycles 5 &11, Follow-up (FU) Month 6, FU Month 12 (1 cycle = 21 days) | EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective \[FP\]) and four symptom scales (systemic side effects \[SE\], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Obtained scores are linearly transformed to a score range of 0-100. High score for functional scale indicated high/better level of functioning/healthy functioning. Higher scores for symptom scales represent higher levels of symptoms/problems. For functional scales, positive change from baseline indicated deterioration in QOL and negative change from baseline indicated an improvement in QOL. For symptom scales, positive change from baseline indicated an improvement in QOL and negative change from baseline indicated a deterioration in QOL. |
| Serum Concentrations of Trastuzumab Emtansine | Pre-infusion on Cycles 1, 2, 4 and 5; 15-30 minutes and 2 hours post-infusion on Cycles 1 and 4; treatment discontinuation/completion visit (up to approximately 64 months) (1 cycle = 21 days) | — |
| Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) | Pre-infusion, 15-30 minutes and 2 hour post-infusion on Cycles 1 and 4 (1 cycle = 21 days) | Concentration of DM1 in plasma was measured through the samples obtained from participants randomized to the trastuzumab emtansine arm. DM1 is an ant-microtubule agent derived from maytansine. In transtuzumab entansine, DM1 is linked to the antibody transtuzumab thus helping the drug to specifically target the HER 2- positive cancer cells. |
| Serum Concentrations of Trastuzumab | Pre-infusion and 15-30 minutes post-infusion on Cycles 1 and 4; Treatment completion/discontinuation visit (up to approximately 64 months) (1 cycle = 21 days) | — |
| Serum Concentrations of Total Trastuzumab | Pre-infusion on Day 1 of Cycles 1, 2, 4, and 5; 15-30 minutes and 2 hours post-infusion on Day 1 of Cycles 1 and 4 (1 cycle = 21 days) | Total trastuzumab is the sum of conjugated and unconjugated trastuzumab. Blood and serum samples were obtained from participants randomized to the trastuzumab arm. |
| Median Duration of Trastuzumab Emtansine Exposure | Up to 12 months | Treatment duration was defined as the time between the first and the last infusion of trastuzumab emtansine. |
Other
| Measure | Time frame | Description |
|---|---|---|
| IDFS Rate at 7 Years | At Year 7 | IDFS event was defined as the first occurrence of any one of the following events: ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site-other than the 2 above-mentioned sites - that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; death attributable to any cause including breast cancer, non-breast cancer or unknown cause . 7-year IDFS rate in ITT population was estimated using KM method and the percentage of participants who were event-free 7 years after randomization was estimated. |
| IDFS Rate at 8 Years | At Year 8 | IDFS event was defined as the first occurrence of any one of the following events: ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site-other than the 2 above-mentioned sites - that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; death attributable to any cause including breast cancer, non-breast cancer or unknown cause . 8-year IDFS rate in ITT population was estimated using KM method and the percentage of participants who were event-free 8 years after randomization was estimated. |
Countries
Argentina, Austria, Belgium, Brazil, Canada, China, Colombia, Czechia, France, Germany, Greece, Guatemala, Hong Kong, Ireland, Israel, Italy, Mexico, Panama, Peru, Serbia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
A total of 1486 participants with human epidermal growth factor receptor 2 (HER2)-positive primary breast cancer who had residual invasive disease in either the breast or axillary lymph nodes took part in the study at 268 investigative sites across 28 countries from April 03, 2013 to May 23, 2024.
Pre-assignment details
Participants received either trastuzumab or trastuzumab emtansine (T-DM1). 1 participant randomized to trastuzumab arm was untreated, later re-randomized to T-DM1 arm & received treatment. Another participant in the trastuzumab arm received 13 cycles of trastuzumab & 1 of T-DM1. Both these participants were included in the trastuzumab ITT population and T-DM1 safety analysis. 1 participant in T-DM1 arm received 9 cycles of trastuzumab & included in trastuzumab safety analysis.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first. | 743 |
| Trastuzumab Emtansine Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first. | 743 |
| Total | 1,486 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 126 | 94 |
| Overall Study | Follow-up Terminated by Sponsor | 441 | 495 |
| Overall Study | Lost to Follow-up | 51 | 50 |
| Overall Study | Other | 9 | 7 |
| Overall Study | Physician Decision | 1 | 7 |
| Overall Study | Withdrawal by Subject | 115 | 90 |
Baseline characteristics
| Characteristic | Trastuzumab | Trastuzumab Emtansine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 68 Participants | 58 Participants | 126 Participants |
| Age, Categorical Between 18 and 65 years | 675 Participants | 685 Participants | 1360 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 107 Participants | 91 Participants | 198 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 543 Participants | 579 Participants | 1122 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 93 Participants | 73 Participants | 166 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 50 Participants | 36 Participants | 86 Participants |
| Race (NIH/OMB) Asian | 64 Participants | 65 Participants | 129 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 21 Participants | 40 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 77 Participants | 69 Participants | 146 Participants |
| Race (NIH/OMB) White | 530 Participants | 551 Participants | 1081 Participants |
| Sex: Female, Male Female | 740 Participants | 741 Participants | 1481 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 126 / 743 | 94 / 743 |
| other Total, other adverse events | 633 / 720 | 719 / 740 |
| serious Total, serious adverse events | 58 / 720 | 94 / 740 |
Outcome results
Primary
Invasive Disease-free Survival (IDFS) Rate at 3 Years
IDFS event was defined as the first occurrence of any one of the following events: ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site-other than the 2 above-mentioned sites - that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; death attributable to any cause including breast cancer, non-breast cancer or unknown cause . 3-year IDFS rate in ITT population was estimated using Kaplan Meier (KM) method and the percentage of participants who were event-free 3 years after randomization was estimated.
Time frame: At Year 3
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Invasive Disease-free Survival (IDFS) Rate at 3 Years | 77.12 percentage of participants |
| Trastuzumab Emtansine | Invasive Disease-free Survival (IDFS) Rate at 3 Years | 88.44 percentage of participants |
p-value: <0.000195% CI: [0.44, 0.66]Log Rank
Secondary
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23)
EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective \[FP\]) and four symptom scales (systemic side effects \[SE\], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Obtained scores are linearly transformed to a score range of 0-100. High score for functional scale indicated high/better level of functioning/healthy functioning. Higher scores for symptom scales represent higher levels of symptoms/problems. For functional scales, positive change from baseline indicated deterioration in QOL and negative change from baseline indicated an improvement in QOL. For symptom scales, positive change from baseline indicated an improvement in QOL and negative change from baseline indicated a deterioration in QOL.
Time frame: Baseline, Cycles 5 &11, Follow-up (FU) Month 6, FU Month 12 (1 cycle = 21 days)
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed per timepoint are unique number of participants out of all the assessed participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Sexual Enjoyment | 50.9 score on a scale | Standard Deviation 28.8 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Body Image | 1.5 score on a scale | Standard Deviation 20.5 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Body Image | 3.4 score on a scale | Standard Deviation 24.4 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Body Image | 3.6 score on a scale | Standard Deviation 25.1 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: Body Image | 6.2 score on a scale | Standard Deviation 27.1 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: FP | 51.3 score on a scale | Standard Deviation 31.2 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: FP | 2.6 score on a scale | Standard Deviation 28.3 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: FP | 6.3 score on a scale | Standard Deviation 30 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: FP | 7.7 score on a scale | Standard Deviation 33.5 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: FP | 8.1 score on a scale | Standard Deviation 31.1 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Body Image | 69.8 score on a scale | Standard Deviation 28.5 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Sexual Enjoyment | 2.3 score on a scale | Standard Deviation 26.4 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Sexual Enjoyment | 4.4 score on a scale | Standard Deviation 27.5 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Sexual Enjoyment | 3.2 score on a scale | Standard Deviation 28.1 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: Sexual Enjoyment | 5.6 score on a scale | Standard Deviation 26 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Sexual Function | 20.2 score on a scale | Standard Deviation 23.6 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Sexual Function | 3.3 score on a scale | Standard Deviation 20 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Sexual Function | 3.1 score on a scale | Standard Deviation 20.8 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Sexual Function | 5.1 score on a scale | Standard Deviation 23.9 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: Sexual Function | 5.9 score on a scale | Standard Deviation 23.7 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Arm Symptoms | 24.6 score on a scale | Standard Deviation 21.1 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Arm Symptoms | -2.8 score on a scale | Standard Deviation 20.9 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Arm Symptoms | -2.6 score on a scale | Standard Deviation 21.2 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Arm Symptoms | -3.0 score on a scale | Standard Deviation 23.5 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: Arm Symptoms | -5.7 score on a scale | Standard Deviation 22.8 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Breast Symptoms | 22.7 score on a scale | Standard Deviation 19.1 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Breast Symptoms | -1.1 score on a scale | Standard Deviation 20.3 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Breast Symptoms | -3.7 score on a scale | Standard Deviation 19.8 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Breast Function | -6.5 score on a scale | Standard Deviation 20 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Follow-up Month 12: Breast Function | -8.3 score on a scale | Standard Deviation 19.9 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Systemic Therapy Side Effects (SE) | 16.7 score on a scale | Standard Deviation 13.7 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Systemic Therapy SE | 0.7 score on a scale | Standard Deviation 13 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Systemic Therapy SE | 1.2 score on a scale | Standard Deviation 12.2 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Systemic Therapy SE | 1.9 score on a scale | Standard Deviation 13.9 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: Systemic Therapy SE | 1.3 score on a scale | Standard Deviation 13.9 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Upset by Hair Loss Item | 40.3 score on a scale | Standard Deviation 35.6 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Upset by Hair Loss Item | -5.1 score on a scale | Standard Deviation 38.1 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Upset by Hair Loss Item | -28.6 score on a scale | Standard Deviation 45 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Upset by Hair Loss Item | -12.0 score on a scale | Standard Deviation 47 |
| Trastuzumab | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: Upset by Hair Loss Item | -2.9 score on a scale | Standard Deviation 37.5 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Upset by Hair Loss Item | -14.3 score on a scale | Standard Deviation 33.9 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Body Image | 67.5 score on a scale | Standard Deviation 28.5 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Arm Symptoms | 24.5 score on a scale | Standard Deviation 21 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Body Image | 4.6 score on a scale | Standard Deviation 22.7 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Systemic Therapy Side Effects (SE) | 16.9 score on a scale | Standard Deviation 14.1 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Body Image | 5.7 score on a scale | Standard Deviation 23.9 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Arm Symptoms | -2.6 score on a scale | Standard Deviation 23 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Body Image | 7.8 score on a scale | Standard Deviation 25.8 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Upset by Hair Loss Item | 50.7 score on a scale | Standard Deviation 38.4 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: Body Image | 6.1 score on a scale | Standard Deviation 27.2 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Arm Symptoms | 0.2 score on a scale | Standard Deviation 24.2 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: FP | 50.1 score on a scale | Standard Deviation 31.7 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Systemic Therapy SE | 5.5 score on a scale | Standard Deviation 15.3 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: FP | 6.5 score on a scale | Standard Deviation 29.9 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Arm Symptoms | -1.3 score on a scale | Standard Deviation 24.2 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: FP | 6.1 score on a scale | Standard Deviation 31.4 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: Upset by Hair Loss Item | -14.3 score on a scale | Standard Deviation 41.6 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: FP | 8.1 score on a scale | Standard Deviation 34.6 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: Arm Symptoms | -1.5 score on a scale | Standard Deviation 22.6 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: FP | 8.2 score on a scale | Standard Deviation 33 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Systemic Therapy SE | 4.2 score on a scale | Standard Deviation 15.4 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Sexual Enjoyment | 52.3 score on a scale | Standard Deviation 28.5 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Breast Symptoms | 21.4 score on a scale | Standard Deviation 17.9 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Sexual Enjoyment | -1.9 score on a scale | Standard Deviation 24.6 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Upset by Hair Loss Item | -17.6 score on a scale | Standard Deviation 39.3 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Sexual Enjoyment | 4.4 score on a scale | Standard Deviation 24.5 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Breast Symptoms | -1.1 score on a scale | Standard Deviation 19.1 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Sexual Enjoyment | 0.3 score on a scale | Standard Deviation 27.5 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Systemic Therapy SE | 1.1 score on a scale | Standard Deviation 15.3 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: Sexual Enjoyment | 1.8 score on a scale | Standard Deviation 26.2 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Breast Symptoms | -0.6 score on a scale | Standard Deviation 19.5 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Baseline: Sexual Function | 22.0 score on a scale | Standard Deviation 23.4 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Upset by Hair Loss Item | -15.2 score on a scale | Standard Deviation 42.1 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 5: Sexual Function | 2.3 score on a scale | Standard Deviation 20 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Breast Function | -2.2 score on a scale | Standard Deviation 19.7 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Cycle 11: Sexual Function | 1.9 score on a scale | Standard Deviation 20.3 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: Systemic Therapy SE | 1.4 score on a scale | Standard Deviation 16.3 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 6: Sexual Function | 4.3 score on a scale | Standard Deviation 23.1 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at Follow-up Month 12: Breast Function | -3.8 score on a scale | Standard Deviation 19.2 |
| Trastuzumab Emtansine | Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) | Change at FU Month 12: Sexual Function | 5.2 score on a scale | Standard Deviation 22.7 |
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30)
The EORTC QLQ-C30 consists of 30 questions which assess five functional domains (physical, role, cognitive, emotional, and social), a global health status/quality of life (GHS/QoL) scale, three symptom scales (fatigue, pain, nausea, and vomiting), five single items (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea), and a perceived financial impact of the disease item. Most questions used a 4-point scale (1= Not at all to 4 = Very much; 2 questions used a 7-point scale \[1 = very poor to 7 = Excellent\]). Obtained scores are linearly transformed to a score range of 0-100, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms. A positive change from baseline indicates improvement.
Time frame: Baseline, Cycles 5 &11, Follow-up (FU) Month 6, FU Month 12 (1 cycle = 21 days)
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed per timepoint are unique number of participants out of all the assessed participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Dyspnea | 3.9 score on a scale | Standard Deviation 24.9 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Nausea/Vomiting | 0.8 score on a scale | Standard Deviation 10.4 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Diarrhea | 8.8 score on a scale | Standard Deviation 17.6 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Nausea/Vomiting | 0.4 score on a scale | Standard Deviation 10.5 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Fatigue | 29.2 score on a scale | Standard Deviation 21.1 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Pain | 22.2 score on a scale | Standard Deviation 22.2 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Appetite Loss | -1.6 score on a scale | Standard Deviation 18.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Pain | 0.0 score on a scale | Standard Deviation 23.2 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Fatigue | 1.1 score on a scale | Standard Deviation 20.1 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Pain | 0.1 score on a scale | Standard Deviation 23.1 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Diarrhea | -1.6 score on a scale | Standard Deviation 19.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Pain | -0.3 score on a scale | Standard Deviation 24.6 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Fatigue | 1.1 score on a scale | Standard Deviation 20.5 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Pain | -1.2 score on a scale | Standard Deviation 25.6 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Constipation | 1.0 score on a scale | Standard Deviation 22.4 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Cognitive Functioning | 83.3 score on a scale | Standard Deviation 20.2 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Fatigue | -1.4 score on a scale | Standard Deviation 21.9 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Cognitive Functioning | -3.8 score on a scale | Standard Deviation 18.4 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Diarrhea | -0.4 score on a scale | Standard Deviation 21.4 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Cognitive Functioning | -5.4 score on a scale | Standard Deviation 21.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Fatigue | -0.1 score on a scale | Standard Deviation 23.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Cognitive Functioning | -4.1 score on a scale | Standard Deviation 22 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Appetite Loss | -0.5 score on a scale | Standard Deviation 17.2 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Cognitive Functioning | -4.9 score on a scale | Standard Deviation 22.2 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Financial Difficulties | 28.6 score on a scale | Standard Deviation 33.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Emotional Functioning | 75.0 score on a scale | Standard Deviation 22 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Diarrhea | -3.4 score on a scale | Standard Deviation 18.5 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Emotional Functioning | -0.4 score on a scale | Standard Deviation 20 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Financial Difficulties | -3.1 score on a scale | Standard Deviation 26.5 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Emotional Functioning | -1.0 score on a scale | Standard Deviation 21.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Constipation | 3.4 score on a scale | Standard Deviation 23.6 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Emotional Functioning | -2.9 score on a scale | Standard Deviation 22 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Financial Difficulties | -5.1 score on a scale | Standard Deviation 27.6 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Emotional Functioning | -2.0 score on a scale | Standard Deviation 22.7 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Diarrhea | -2.8 score on a scale | Standard Deviation 18.9 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Physical Functioning | 84.5 score on a scale | Standard Deviation 15.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Financial Difficulties | -8.4 score on a scale | Standard Deviation 28.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Physical Functioning | 0.3 score on a scale | Standard Deviation 12.9 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Appetite Loss | 0.5 score on a scale | Standard Deviation 20.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Physical Functioning | 1.9 score on a scale | Standard Deviation 14.2 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Financial Difficulties | -10.9 score on a scale | Standard Deviation 30.5 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Physical Functioning | 2.8 score on a scale | Standard Deviation 15.4 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Dyspnea | 12.7 score on a scale | Standard Deviation 20.7 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Physical Functioning | 2.7 score on a scale | Standard Deviation 14.5 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Insomnia | 30.6 score on a scale | Standard Deviation 30.8 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Role Functioning | 77.5 score on a scale | Standard Deviation 25 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Constipation | 4.1 score on a scale | Standard Deviation 23.7 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Role Functioning | 2.0 score on a scale | Standard Deviation 24.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Insomnia | 1.9 score on a scale | Standard Deviation 28.4 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Role Functioning | 4.0 score on a scale | Standard Deviation 24.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Dyspnea | 2.3 score on a scale | Standard Deviation 21.9 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Role Functioning | 7.4 score on a scale | Standard Deviation 25.8 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Insomnia | 2.4 score on a scale | Standard Deviation 29.9 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Role Functioning | 8.0 score on a scale | Standard Deviation 27.5 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Appetite Loss | 1.0 score on a scale | Standard Deviation 18.7 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Social Functioning | 77.1 score on a scale | Standard Deviation 24.1 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Insomnia | 1.8 score on a scale | Standard Deviation 31.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Social Functioning | 4.0 score on a scale | Standard Deviation 22.5 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Dyspnea | 2.8 score on a scale | Standard Deviation 21.2 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Social Functioning | 5.8 score on a scale | Standard Deviation 24 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Insomnia | 0.3 score on a scale | Standard Deviation 30.4 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Social Functioning | 8.5 score on a scale | Standard Deviation 23.7 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Constipation | 3.2 score on a scale | Standard Deviation 23.2 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Social Functioning | 9.5 score on a scale | Standard Deviation 25.1 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Nausea/Vomiting | 3.3 score on a scale | Standard Deviation 9 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Global Health Status | 71.2 score on a scale | Standard Deviation 19.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Dyspnea | 3.3 score on a scale | Standard Deviation 22.8 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Global Health Status | 0.6 score on a scale | Standard Deviation 18.9 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Nausea/Vomiting | 1.5 score on a scale | Standard Deviation 11.2 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Global Health Status | 1.7 score on a scale | Standard Deviation 17.8 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Constipation | 9.8 score on a scale | Standard Deviation 20.2 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Global Health Status | 2.5 score on a scale | Standard Deviation 19.3 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Nausea/Vomiting | 1.3 score on a scale | Standard Deviation 12.8 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Global Health Status | 3.2 score on a scale | Standard Deviation 19.5 |
| Trastuzumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Appetite Loss | 7.9 score on a scale | Standard Deviation 17.4 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Global Health Status | 2.8 score on a scale | Standard Deviation 20.1 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Appetite Loss | 7.1 score on a scale | Standard Deviation 16.4 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Appetite Loss | 6.5 score on a scale | Standard Deviation 23.7 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Appetite Loss | 2.9 score on a scale | Standard Deviation 20.2 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Appetite Loss | -1.7 score on a scale | Standard Deviation 19.9 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Appetite Loss | -1.9 score on a scale | Standard Deviation 20.1 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Constipation | 9.5 score on a scale | Standard Deviation 19 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Constipation | 4.6 score on a scale | Standard Deviation 22.6 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Constipation | 7.3 score on a scale | Standard Deviation 23.1 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Constipation | 3.7 score on a scale | Standard Deviation 23.3 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Constipation | 4.3 score on a scale | Standard Deviation 24.6 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Diarrhea | 6.4 score on a scale | Standard Deviation 14.9 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Diarrhea | -1.5 score on a scale | Standard Deviation 19.5 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Diarrhea | -2.4 score on a scale | Standard Deviation 17.5 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Diarrhea | -1.9 score on a scale | Standard Deviation 18.3 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Diarrhea | -1.6 score on a scale | Standard Deviation 18.4 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Dyspnea | 11.0 score on a scale | Standard Deviation 18.8 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Dyspnea | 4.1 score on a scale | Standard Deviation 22.4 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Dyspnea | 2.7 score on a scale | Standard Deviation 20.4 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Dyspnea | 3.8 score on a scale | Standard Deviation 22.7 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Dyspnea | 5.3 score on a scale | Standard Deviation 22.4 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Fatigue | 28.0 score on a scale | Standard Deviation 20 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Fatigue | 5.5 score on a scale | Standard Deviation 19.7 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Fatigue | 3.8 score on a scale | Standard Deviation 21.3 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Fatigue | -0.1 score on a scale | Standard Deviation 22.2 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Fatigue | -0.1 score on a scale | Standard Deviation 22.1 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Financial Difficulties | 27.6 score on a scale | Standard Deviation 31.9 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Financial Difficulties | -3.0 score on a scale | Standard Deviation 28 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Financial Difficulties | -1.7 score on a scale | Standard Deviation 28.7 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Financial Difficulties | -6.5 score on a scale | Standard Deviation 30.6 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Financial Difficulties | -7.3 score on a scale | Standard Deviation 31 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Insomnia | 30.6 score on a scale | Standard Deviation 29.2 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Insomnia | 1.3 score on a scale | Standard Deviation 29.7 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Insomnia | 1.5 score on a scale | Standard Deviation 30.3 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Insomnia | -0.9 score on a scale | Standard Deviation 32.1 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Insomnia | 0.7 score on a scale | Standard Deviation 31.7 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Nausea/Vomiting | 2.8 score on a scale | Standard Deviation 8 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Nausea/Vomiting | 3.2 score on a scale | Standard Deviation 12.5 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Nausea/Vomiting | 3.0 score on a scale | Standard Deviation 11.8 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Nausea/Vomiting | 0.2 score on a scale | Standard Deviation 11.1 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Nausea/Vomiting | 1.2 score on a scale | Standard Deviation 10.9 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Pain | 22.6 score on a scale | Standard Deviation 22.8 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Pain | 1.8 score on a scale | Standard Deviation 23.9 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Pain | 2.1 score on a scale | Standard Deviation 24.4 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Pain | -0.5 score on a scale | Standard Deviation 24.3 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Pain | -0.8 score on a scale | Standard Deviation 25.4 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Cognitive Functioning | 84.4 score on a scale | Standard Deviation 19 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Cognitive Functioning | -4.5 score on a scale | Standard Deviation 18.7 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Cognitive Functioning | -5.3 score on a scale | Standard Deviation 19.6 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Cognitive Functioning | -6.1 score on a scale | Standard Deviation 21.6 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Cognitive Functioning | -6.9 score on a scale | Standard Deviation 21.7 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Emotional Functioning | 75.2 score on a scale | Standard Deviation 21.2 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Emotional Functioning | -1.3 score on a scale | Standard Deviation 21.3 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Emotional Functioning | 0.1 score on a scale | Standard Deviation 22 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Emotional Functioning | -0.8 score on a scale | Standard Deviation 23.3 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Emotional Functioning | -1.6 score on a scale | Standard Deviation 23.5 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Physical Functioning | 85.8 score on a scale | Standard Deviation 14.1 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Physical Functioning | -1.6 score on a scale | Standard Deviation 12.7 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Physical Functioning | -0.6 score on a scale | Standard Deviation 14.6 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Physical Functioning | 0.7 score on a scale | Standard Deviation 15.1 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Physical Functioning | 0.8 score on a scale | Standard Deviation 14.5 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Role Functioning | 78.6 score on a scale | Standard Deviation 23.3 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Role Functioning | -0.2 score on a scale | Standard Deviation 24.1 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Role Functioning | 0.6 score on a scale | Standard Deviation 24.5 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Role Functioning | 3.6 score on a scale | Standard Deviation 26.7 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Role Functioning | 4.6 score on a scale | Standard Deviation 25.5 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Social Functioning | 76.8 score on a scale | Standard Deviation 23.2 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Social Functioning | 1.6 score on a scale | Standard Deviation 23.8 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Social Functioning | 2.5 score on a scale | Standard Deviation 23.6 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Social Functioning | 6.5 score on a scale | Standard Deviation 26.1 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 12: Social Functioning | 7.4 score on a scale | Standard Deviation 26.4 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Baseline: Global Health Status | 71.4 score on a scale | Standard Deviation 18 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 5: Global Health Status | -1.9 score on a scale | Standard Deviation 19.6 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at Cycle 11: Global Health Status | -0.5 score on a scale | Standard Deviation 19.9 |
| Trastuzumab Emtansine | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) | Change at FU Month 6: Global Health Status | 2.0 score on a scale | Standard Deviation 19.2 |
Secondary
DFS Rate at 7 Years
DFS was defined as the time between randomization and the date of the first occurrence of an IDFS event including SPNBC event or contralateral or ipsilateral DCIS. IDFS event was defined as outlined in the description for IDFS rate OM number 1. 7-year DFS rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 7 years after randomization was estimated.
Time frame: At Year 7
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | DFS Rate at 7 Years | 66.03 percentage of participants |
| Trastuzumab Emtansine | DFS Rate at 7 Years | 79.37 percentage of participants |
p-value: <0.000195% CI: [0.48, 0.7]Log Rank
Secondary
DFS Rate at 8 Years
DFS was defined as the time between randomization and the date of the first occurrence of an IDFS event including SPNBC event or contralateral or ipsilateral DCIS. IDFS event was defined as outlined in the description for IDFS rate OM number 1. 8-year DFS rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 8 years after randomization was estimated.
Time frame: At Year 8
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | DFS Rate at 8 Years | 63.49 percentage of participants |
| Trastuzumab Emtansine | DFS Rate at 8 Years | 77.14 percentage of participants |
p-value: <0.000195% CI: [0.48, 0.7]Log Rank
Secondary
Disease-free Survival (DFS) Rate at 3 Years
DFS was defined as the time between randomization and the date of the first occurrence of an IDFS event including SPNBC event or contralateral or ipsilateral ductal carcinoma in situ (DCIS). IDFS event was defined as outlined in the description for IDFS rate OM number 1. 3-year DFS rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 3 years after randomization was estimated.
Time frame: At Year 3
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Disease-free Survival (DFS) Rate at 3 Years | 76.98 percentage of participants |
| Trastuzumab Emtansine | Disease-free Survival (DFS) Rate at 3 Years | 87.59 percentage of participants |
p-value: <0.000195% CI: [0.48, 0.7]Log Rank
Secondary
Distant Recurrence-free Interval (DRFI) Rate at 3 Years
DRFI was defined as the time between randomization and the date of distant breast cancer recurrence. 3-year DRFI event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 3 years after randomization was estimated.
Time frame: At Year 3
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Distant Recurrence-free Interval (DRFI) Rate at 3 Years | 83.26 percentage of participants |
| Trastuzumab Emtansine | Distant Recurrence-free Interval (DRFI) Rate at 3 Years | 89.95 percentage of participants |
p-value: <0.000195% CI: [0.47, 0.76]Log Rank
Secondary
DRFI Rate at 7 Years
DRFI was defined as the time between randomization and the date of distant breast cancer recurrence. 7-year DRFI event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 7 years after randomization was estimated.
Time frame: At Year 7
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | DRFI Rate at 7 Years | 76.22 percentage of participants |
| Trastuzumab Emtansine | DRFI Rate at 7 Years | 84.55 percentage of participants |
p-value: <0.000195% CI: [0.47, 0.76]Log Rank
Secondary
DRFI Rate at 8 Years
DRFI was defined as the time between randomization and the date of distant breast cancer recurrence. 8-year DRFI event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 8 years after randomization was estimated.
Time frame: At Year 8
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | DRFI Rate at 8 Years | 74.28 percentage of participants |
| Trastuzumab Emtansine | DRFI Rate at 8 Years | 83.82 percentage of participants |
p-value: <0.000195% CI: [0.47, 0.76]Log Rank
Secondary
IDFS Including Second Primary Non-breast Cancer (SPNBC) Rate at 3 Years
IDFS including SPNBC was defined the same way as IDFS but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and carcinoma in situ \[CIS\] of any site). IDFS event was defined as outlined in the description for IDFS rate outcome measure (OM) number 1. 3-year IDFS including SPNBC rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 3 years after randomization was estimated.
Time frame: At Year 3
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | IDFS Including Second Primary Non-breast Cancer (SPNBC) Rate at 3 Years | 76.98 percentage of participants |
| Trastuzumab Emtansine | IDFS Including Second Primary Non-breast Cancer (SPNBC) Rate at 3 Years | 87.87 percentage of participants |
p-value: <0.000195% CI: [0.46, 0.69]Log Rank
Secondary
IDFS Including SPNBC Rate at 7 Years
IDFS including SPNBC was defined the same way as IDFS but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and CIS of any site). IDFS event was defined as outlined in the description for IDFS rate OM number 1. 7-year IDFS including SPNBC rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 7 years after randomization was estimated.
Time frame: At Year 7
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | IDFS Including SPNBC Rate at 7 Years | 66.19 percentage of participants |
| Trastuzumab Emtansine | IDFS Including SPNBC Rate at 7 Years | 79.81 percentage of participants |
p-value: <0.000195% CI: [0.46, 0.69]Log Rank
Secondary
IDFS Including SPNBC Rate at 8 Years
IDFS including SPNBC was defined the same way as IDFS but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and CIS of any site). IDFS event was defined as outlined in the description for IDFS rate OM number 1. 8-year IDFS including SPNBC rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 8 years after randomization was estimated.
Time frame: At Year 8
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | IDFS Including SPNBC Rate at 8 Years | 63.65 percentage of participants |
| Trastuzumab Emtansine | IDFS Including SPNBC Rate at 8 Years | 77.76 percentage of participants |
p-value: <0.000195% CI: [0.46, 0.69]Log Rank
Secondary
Median Duration of Trastuzumab Emtansine Exposure
Treatment duration was defined as the time between the first and the last infusion of trastuzumab emtansine.
Time frame: Up to 12 months
Population: SE population included all randomized participants who received any amount of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab | Median Duration of Trastuzumab Emtansine Exposure | 10 months |
Secondary
Number of Participants Who Discontinued Treatment Due to AEs
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants were treated for up to 14 cycles (1 cycle = 21 days).
Time frame: Up to approximately 9.6 months
Population: SE population included all randomized participants who received any amount of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trastuzumab | Number of Participants Who Discontinued Treatment Due to AEs | 15 Participants |
| Trastuzumab Emtansine | Number of Participants Who Discontinued Treatment Due to AEs | 134 Participants |
Secondary
Number of Participants With AEs and SAEs Leading to Death
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was any AE that met any of the following criteria: fatal (i.e., the AE actually causes or leads to death); life-threatening (i.e., the AE, in the view of the investigator, placed the participant at immediate risk of death); required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity (i.e., the AE results in substantial disruption of the participant's ability to conduct normal life functions); congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug; significant medical event in the investigator's judgment.
Time frame: From signing of informed consent till end of follow up (up to approximately 131 months)
Population: SE population included all randomized participants who received any amount of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trastuzumab | Number of Participants With AEs and SAEs Leading to Death | 0 Participants |
| Trastuzumab Emtansine | Number of Participants With AEs and SAEs Leading to Death | 1 Participants |
Secondary
Number of Participants With Positive ADAs to Trastuzumab
ADA-positive participants after drug administration were determined for participants exposed to trastuzumab. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 t.u. greater than the baseline titer result. The total number of participants who developed ADAs to trastuzumab was determined by summing the ADA-positive participants across all timepoints.
Time frame: Baseline (Day1 of Cycle1) and Post Baseline (Day 1 of Cycle 4 up to 3-4 months after last dose of the drug [up to approximately 13.6 months])
Population: SE Population included all randomized participants who received any amount of study treatment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Trastuzumab | Number of Participants With Positive ADAs to Trastuzumab | Baseline | 11 Participants |
| Trastuzumab | Number of Participants With Positive ADAs to Trastuzumab | Post-baseline | 15 Participants |
Secondary
Number of Participants With Positive Anti-drug Antibodies (ADAs) to Trastuzumab Emtansine
ADA-positive participants after drug administration were determined for participants exposed to trastuzumab emtansine. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the baseline titer result. The total number of participants who developed ADAs to trastuzumab emtansine was determined by summing the ADA-positive participants across all timepoints.
Time frame: Baseline (Day1 of Cycle1) and Post Baseline (Day 1 of Cycle 4 up to 3-4 months after last dose of the drug [up to approximately 13.6 months])
Population: SE Population included all randomized participants who received any amount of study treatment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Trastuzumab | Number of Participants With Positive Anti-drug Antibodies (ADAs) to Trastuzumab Emtansine | Baseline | 17 Participants |
| Trastuzumab | Number of Participants With Positive Anti-drug Antibodies (ADAs) to Trastuzumab Emtansine | Post-baseline | 16 Participants |
Secondary
OS Rate at 7 Years
OS was defined as the time from randomization to death due to any cause. 7-year OS event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 7 years after randomization was estimated.
Time frame: At Year 7
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | OS Rate at 7 Years | 84.38 percentage of participants |
| Trastuzumab Emtansine | OS Rate at 7 Years | 89.07 percentage of participants |
p-value: 0.008295% CI: [0.53, 0.91]Log Rank
Secondary
OS Rate at 8 Years
OS was defined as the time from randomization to death due to any cause. 8-year OS event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 8 years after randomization was estimated.
Time frame: At Year 8
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | OS Rate at 8 Years | 81.91 percentage of participants |
| Trastuzumab Emtansine | OS Rate at 8 Years | 87.16 percentage of participants |
p-value: 0.008295% CI: [0.53, 0.91]Log Rank
Secondary
Overall Survival (OS) Rate at 5 Years
OS was defined as the time from randomization to death due to any cause. 5-year OS event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 5 years after randomization was estimated.
Time frame: At Year 5
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Overall Survival (OS) Rate at 5 Years | 87.71 percentage of participants |
| Trastuzumab Emtansine | Overall Survival (OS) Rate at 5 Years | 91.40 percentage of participants |
p-value: 0.008295% CI: [0.53, 0.91]Log Rank
Secondary
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE=any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. AE can therefore be any unfavorable & unintended sign (including abnormal laboratory finding), symptom/disease temporally associated with use of a medicinal product, whether or not considered related to medicinal product. SAE=any AE that met any given criteria: fatal (i.e. AE causes/leads to death); life-threatening (i.e. AE, in view of investigator, placed the participant at immediate risk of death); required/prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity (i.e. AE results in substantial disruption of participant's ability to conduct normal life functions); congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug; significant medical event in investigator's judgment. Percentages have been rounded off.
Time frame: From signing of informed consent till end of follow up (up to approximately 131 months)
Population: SE population included all randomized participants who received any amount of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 93.3 percentage of participants |
| Trastuzumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 8.1 percentage of participants |
| Trastuzumab Emtansine | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 98.8 percentage of participants |
| Trastuzumab Emtansine | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 12.7 percentage of participants |
Secondary
Percentage of Participants With Cardiac Events as Adjudicated by the Cardiac Review Committee
Cardiac events were defined as death from cardiac cause or severe congestive heart failure (New York Heart Association \[NYHA\] Class III or IV) with a decrease in left ventricular ejection fraction (LVEF) of 10 percentage points or more from baseline to an LVEF of \< 50%. Other cardiac-related events (e.g., any symptomatic congestive heart failure \[CHF\] associated with a 10% drop in LVEF to \< 50%; asymptomatic declines in LVEF requiring dose delay) were summarized as adjudicated by the Cardiac Review Committee. Percentages have been rounded off.
Time frame: Up to approximately 126 months
Population: SE population included all randomized participants who received any amount of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Percentage of Participants With Cardiac Events as Adjudicated by the Cardiac Review Committee | 4.2 percentage of participants |
| Trastuzumab Emtansine | Percentage of Participants With Cardiac Events as Adjudicated by the Cardiac Review Committee | 3.1 percentage of participants |
Secondary
Percentage of Participants With Hepatotoxicity Events as Adjudicated by the Hepatic Review Committee
Hepatotoxicity events were summarized by treatment arm. Hepatotoxicity events were assessed using liver function laboratory test (LFT) results which included the analysis of baseline and post-baseline levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBILI), and alkaline phosphatase (ALK). Hepatic events, as adjudicated by the Hepatic Review Committee, are summarized. Percentages have been rounded off.
Time frame: Up to approximately 64 months
Population: SE population included all randomized participants who received any amount of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Percentage of Participants With Hepatotoxicity Events as Adjudicated by the Hepatic Review Committee | 0.1 percentage of participants |
| Trastuzumab Emtansine | Percentage of Participants With Hepatotoxicity Events as Adjudicated by the Hepatic Review Committee | 0.5 percentage of participants |
Secondary
Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1)
Concentration of DM1 in plasma was measured through the samples obtained from participants randomized to the trastuzumab emtansine arm. DM1 is an ant-microtubule agent derived from maytansine. In transtuzumab entansine, DM1 is linked to the antibody transtuzumab thus helping the drug to specifically target the HER 2- positive cancer cells.
Time frame: Pre-infusion, 15-30 minutes and 2 hour post-infusion on Cycles 1 and 4 (1 cycle = 21 days)
Population: PK-evaluable population included all participants who received atleast 1 dose of trastuzumab emtansine and had at least one evaluable post dose PK sample. Overall number analyzed is the number of participants with data available for analysis. Number analyzed per timepoint are unique number of participants out of all the assessed participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab | Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) | Pre-infusion on Cycle 1 | NA nanograms per milliliter (ng/mL) | — |
| Trastuzumab | Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) | 15-30 minutes post-infusion on Cycle 1 | 4.21 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 57.4 |
| Trastuzumab | Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) | 2 hours post-infusion on Cycle 1 | 3.44 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 38.2 |
| Trastuzumab | Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) | Pre-infusion on Cycle 4 | 0.372 nanograms per milliliter (ng/mL) | — |
| Trastuzumab | Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) | 15-30 minutes post-infusion on Cycle 4 | 4.81 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48.8 |
| Trastuzumab | Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) | 2 hours post-infusion on Cycle 4 | 3.70 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
Secondary
Serum Concentrations of Total Trastuzumab
Total trastuzumab is the sum of conjugated and unconjugated trastuzumab. Blood and serum samples were obtained from participants randomized to the trastuzumab arm.
Time frame: Pre-infusion on Day 1 of Cycles 1, 2, 4, and 5; 15-30 minutes and 2 hours post-infusion on Day 1 of Cycles 1 and 4 (1 cycle = 21 days)
Population: PK-evaluable population included all participants who received at least 1 dose of trastuzumab and had at least one evaluable post dose PK sample. Overall number analyzed is the number of participants with data available for analysis. Number analyzed per timepoint are unique number of participants out of all the assessed participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab | Serum Concentrations of Total Trastuzumab | Pre-infusion on Cycle 1 | NA ug/mL | — |
| Trastuzumab | Serum Concentrations of Total Trastuzumab | 15-30 minutes post-infusion on Cycle 1 | 71.8 ug/mL | Geometric Coefficient of Variation 154.7 |
| Trastuzumab | Serum Concentrations of Total Trastuzumab | 2 hours post-infusion on Cycle 1 | 81.4 ug/mL | Geometric Coefficient of Variation 74.3 |
| Trastuzumab | Serum Concentrations of Total Trastuzumab | Pre-infusion on Cycle 2 | 7.93 ug/mL | Geometric Coefficient of Variation 256.8 |
| Trastuzumab | Serum Concentrations of Total Trastuzumab | Pre-infusion on Cycle 4 | 13.7 ug/mL | Geometric Coefficient of Variation 78 |
| Trastuzumab | Serum Concentrations of Total Trastuzumab | 15-30 minutes post-infusion on Cycle 4 | 76.9 ug/mL | Geometric Coefficient of Variation 46.5 |
| Trastuzumab | Serum Concentrations of Total Trastuzumab | 2 hours post-infusion on Cycle 4 | 81.5 ug/mL | Geometric Coefficient of Variation 34 |
| Trastuzumab | Serum Concentrations of Total Trastuzumab | Pre-infusion on Cycle 5 | 8.90 ug/mL | Geometric Coefficient of Variation 125 |
Secondary
Serum Concentrations of Trastuzumab
Time frame: Pre-infusion and 15-30 minutes post-infusion on Cycles 1 and 4; Treatment completion/discontinuation visit (up to approximately 64 months) (1 cycle = 21 days)
Population: PK-evaluable population included all participants who received at least 1 dose of trastuzumab and had at least one evaluable post dose PK sample. Overall number analyzed is the number of participants with data available for analysis. Number analyzed per timepoint are unique number of participants out of all the assessed participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab | Serum Concentrations of Trastuzumab | Pre-infusion on Cycle 1 | NA ug/mL | — |
| Trastuzumab | Serum Concentrations of Trastuzumab | 15-30 minutes post-infusion on Cycle 1 | 208 ug/mL | Geometric Coefficient of Variation 43.1 |
| Trastuzumab | Serum Concentrations of Trastuzumab | Pre-infusion on Cycle 4 | 64.8 ug/mL | Geometric Coefficient of Variation 60.6 |
| Trastuzumab | Serum Concentrations of Trastuzumab | 15-30 minutes post-infusion on Cycle 4 | 218 ug/mL | Geometric Coefficient of Variation 47.2 |
| Trastuzumab | Serum Concentrations of Trastuzumab | Treatment Completion/Discontinuation | 58.7 ug/mL | Geometric Coefficient of Variation 86.3 |
Secondary
Serum Concentrations of Trastuzumab Emtansine
Time frame: Pre-infusion on Cycles 1, 2, 4 and 5; 15-30 minutes and 2 hours post-infusion on Cycles 1 and 4; treatment discontinuation/completion visit (up to approximately 64 months) (1 cycle = 21 days)
Population: Pharmacokinetic (PK)-evaluable population included all participants who received at least 1 dose of trastuzumab emtansine and had at least one evaluable post dose PK sample. Overall number analyzed is the number of participants with data available for analysis. Number analyzed per timepoint are unique number of participants out of all the assessed participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab | Serum Concentrations of Trastuzumab Emtansine | 2 hours post-infusion on Cycle 1 | 67.4 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 60 |
| Trastuzumab | Serum Concentrations of Trastuzumab Emtansine | Pre-infusion on Cycle 2 | 1.69 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 110.7 |
| Trastuzumab | Serum Concentrations of Trastuzumab Emtansine | Pre-infusion on Cycle 1 | NA micrograms per milliliter (ug/mL) | — |
| Trastuzumab | Serum Concentrations of Trastuzumab Emtansine | 15-30 minutes post-infusion on Cycle 1 | 63.0 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 101.8 |
| Trastuzumab | Serum Concentrations of Trastuzumab Emtansine | Pre-infusion on Cycle 4 | 1.73 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 95.7 |
| Trastuzumab | Serum Concentrations of Trastuzumab Emtansine | 15-30 minutes post-infusion on Cycle 4 | 68.5 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 59.4 |
| Trastuzumab | Serum Concentrations of Trastuzumab Emtansine | 2 hours post-infusion on Cycle 4 | 66.4 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 71 |
| Trastuzumab | Serum Concentrations of Trastuzumab Emtansine | Pre-infusion on Cycle 5 | 1.67 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 99.3 |
| Trastuzumab | Serum Concentrations of Trastuzumab Emtansine | Treatment Completion/Discontinuation | 0.323 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 265.3 |
Other Pre-specified
IDFS Rate at 7 Years
IDFS event was defined as the first occurrence of any one of the following events: ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site-other than the 2 above-mentioned sites - that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; death attributable to any cause including breast cancer, non-breast cancer or unknown cause . 7-year IDFS rate in ITT population was estimated using KM method and the percentage of participants who were event-free 7 years after randomization was estimated.
Time frame: At Year 7
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | IDFS Rate at 7 Years | 67.11 percentage of participants |
| Trastuzumab Emtansine | IDFS Rate at 7 Years | 80.82 percentage of participants |
p-value: <0.000195% CI: [0.44, 0.66]Log Rank
Other Pre-specified
IDFS Rate at 8 Years
IDFS event was defined as the first occurrence of any one of the following events: ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site-other than the 2 above-mentioned sites - that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; death attributable to any cause including breast cancer, non-breast cancer or unknown cause . 8-year IDFS rate in ITT population was estimated using KM method and the percentage of participants who were event-free 8 years after randomization was estimated.
Time frame: At Year 8
Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | IDFS Rate at 8 Years | 64.57 percentage of participants |
| Trastuzumab Emtansine | IDFS Rate at 8 Years | 79.11 percentage of participants |
p-value: <0.000195% CI: [0.44, 0.66]Log Rank