Metastatic Breast Cancer
Conditions
Brief summary
This is a Phase III, randomized, multicenter, multinational, two-arm, open-label clinical trial to investigate a first-line treatment of participants with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer. The study will enroll patients with HER2-positive, unresectable, locally advanced breast cancer (BC) if they have recurrent disease or progressive disease (PD) despite primary multi-modality therapy, and/or metastatic BC if they have not received prior chemotherapy for their metastatic disease. Eligible participants at up to approximately 40 sites in the Asia-Pacific region will be randomized in a 2:1 ratio to receive trastuzumab emtansine (Arm A) or trastuzumab plus docetaxel (Arm B). All study drugs will be administered at in-clinic visits occurring every three weeks during the treatment phase. Trastuzumab plus docetaxel was chosen as the comparator in the control group (Arm B), as it represents a common first-line treatment option used in this patient population in China and other Asia-Pacific countries.
Interventions
DRUGTrastuzumab
For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W.
DRUGTrastuzumab Emtansine
Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.
DRUGDocetaxel
Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Sponsors
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
* Age \>/= 18 years * HER2-positive disease, as defined by an immunohistochemistry test score of 3+ and/or in situ hybridization positivity, prospectively confirmed by a Sponsor-designated central laboratory prior to enrollment * Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease appropriate for chemotherapy * Patients must have measurable and/or non-measurable disease that is evaluable per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1 * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Adequate organ function * For women of childbearing potential and men with partners of childbearing potential, agreement by the patient and/or partner to use two adequate non-hormonal forms of contraception during treatment and for at least 6 months after the last dose of study drug
Exclusion criteria
* Pregnancy or lactation * Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; bone fractures, except bone fractures because of disease under study) * Currently known active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) * Major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment * Current peripheral neuropathy Grade \>/= 2 per National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE, v4.0) * History of systemic anti-cancer therapy after the diagnosis of metastatic breast cancer (MBC) or for recurrent locally advanced disease, with the exception of prior hormonal regimens for recurrent locally advanced disease or MBC * An interval of \< 12 months after the last dose of vinca alkaloid or taxane chemotherapy (i.e., for treatment of early stage, non-metastatic disease) * Hormonal therapy \< 7 days prior to randomization * Trastuzumab \< 21 days prior to randomization * Lapatinib \</= 14 days prior to randomization * Prior trastuzumab emtansine therapy * Treatment with any other anti-cancer therapy/investigational drug (not defined above) within 21 days prior to randomization * 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 malignancies with an expected curative outcome * Current chronic daily treatment with corticosteroids (dose \> 10 mg/day methylprednisone equivalent) * History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab, murine proteins, docetaxel or paclitaxel * Known hypersensitivity any of the study drugs, including excipients, or any drugs formulated in polysorbate 80
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | At time of clinical data cut-off (up to 20 months) | PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions. |
| Safety: Percentage of Participants With Adverse Events (AEs) | At time of clinical data cut-off (up to 20 months) | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. |
| Safety: Percentage of Participants With Grade 3 and 4 AEs | At time of clinical data cut-off (up to 20 months) | Grade 3 and 4 AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0. Grade 3 was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living, including bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Grade 4 was defined as life-threatening consequences; urgent intervention indicated. |
| Percentage of Participants With Adverse Events Leading to Treatment Discontinuation | At time of clinical data cut-off (up to 20 months) | — |
| Safety: Percentage of Participants With Adverse Events Leading to Treatment Interruption | At time of clinical data cut-off (up to 20 months) | — |
| Safety: Percentage of Participants With Adverse Events Leading to Dose Reduction | At time of clinical data cut-off (up to 20 months) | — |
| Safety: Percentage of Participants With Significant Decline in Left Ventricular Ejection Fraction (LVEF) | At time of clinical data cut-off (up to 20 months) | Significant decline in LVEF was defined as LVEF below 50% and decrease from baseline of 15% points or more. Echocardiogram or multiple-gated acquisition (MUGA) scan was used to assess LVEF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | On the first Day of each 21-day Cycle (Day 1, 22, 43, etc.) and at study drug completion or discontinuation visit (up to 20 months) | The FACT-B (version 4) is a self-reported instrument which measures health-related quality of life (HRQOL) of participants with breast cancer.The FACT-B includes the breast cancer sub-scale (BCS) and is comprised of nine items specific to assessing patients' HRQOL in breast cancer. |
| Overall Survival (OS) | At time of clinical data cut-off (up to 20 months) | OS was defined as the time from the date of randomization to the date of death from any cause. |
| Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Days 1 and 8 of Cycles 1 and 2 and on the first day of each subsequent 21-day cycle thereafter as well as at study drug completion or discontinuation visit (up to 20 months) | The FACT - Taxane is a self-reported instrument which measures the HRQOL of participants receiving taxane containing chemotherapy. The FACT-Taxane consists of 16 items and was designed to assess the impact of taxane treatment-related symptoms from the participant's perspective. |
| One-Year Survival Rate | At 12 months | One-year survival rate as determined by Kaplan-Meier estimates. |
| OS Truncated at 2 Years | At 24 months | OS truncated at 2 years was defined as the time from the date of randomization to the date of death from any cause, with deaths occurring beyond 2 years after the participant's randomization date censored at 2 years. |
| Objective Response Rate (ORR) | At time of clinical data cut-off (up to 20 months) | ORR was defined as percentage of participants with partial response (PR) or complete response (CR) determined on the basis of investigator assessments with the use of RECIST v1.1. Tumor assessments were performed with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis. CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response Rate (OR) = CR + PR. |
| Duration of Response (DOR) | At time of clinical data cut-off (up to 20 months) | DOR was defined as the time from the date of initial confirmed PR or CR to the date of disease progression or death within the study. CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the longest diameter of target lesions. Disease progression was defined according to RECIST, v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions. |
| Pharmacokinetics: Serum Concentrations of Study Medications | Day 1, Cycle 1 (Day 1), Day 1, Cycle 2 (Day 22), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months) | Pharmacokinetic (PK) parameters were to be determined in a subset of participants. PK samples from the first 100 Chinese participants were planned to be collected. |
| Immunogenicity: Percentage of Positive Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine | Day 1, Cycle 1 (Day 1), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months) | — |
Countries
Malaysia, South Korea, Taiwan, Thailand
Participant flow
Pre-assignment details
Only 49 participants of the originally planned 561 participants were enrolled in the study at the time of study termination.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Trastuzumab Emtansine Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first.
Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W. | 34 |
| Arm B: Trastuzumab + Docetaxel Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first.
Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W.
Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W. | 15 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Other | 3 | 0 |
| Overall Study | Study Terminated by Sponsor | 18 | 12 |
| Overall Study | Withdrawal by Subject | 11 | 3 |
Baseline characteristics
| Characteristic | Arm A: Trastuzumab Emtansine | Arm B: Trastuzumab + Docetaxel | Total |
|---|---|---|---|
| Age, Continuous | 53.7 years STANDARD_DEVIATION 9.5 | 51.7 years STANDARD_DEVIATION 11.1 | 53.1 years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 34 Participants | 15 Participants | 49 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 34 | 15 / 15 |
| serious Total, serious adverse events | 8 / 34 | 5 / 15 |
Outcome results
Primary
Percentage of Participants With Adverse Events Leading to Treatment Discontinuation
Time frame: At time of clinical data cut-off (up to 20 months)
Population: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Trastuzumab Emtansine | Percentage of Participants With Adverse Events Leading to Treatment Discontinuation | 14.7 percentage of participants |
| Arm B: Trastuzumab + Docetaxel | Percentage of Participants With Adverse Events Leading to Treatment Discontinuation | 20.0 percentage of participants |
Primary
Progression-Free Survival (PFS)
PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions.
Time frame: At time of clinical data cut-off (up to 20 months)
Population: The intent-to-treat (ITT) population included all randomized participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Trastuzumab Emtansine | Progression-Free Survival (PFS) | 10.3 months |
| Arm B: Trastuzumab + Docetaxel | Progression-Free Survival (PFS) | 8.2 months |
Primary
Safety: Percentage of Participants With Adverse Events (AEs)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: At time of clinical data cut-off (up to 20 months)
Population: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Trastuzumab Emtansine | Safety: Percentage of Participants With Adverse Events (AEs) | 94.1 percentage of participants |
| Arm B: Trastuzumab + Docetaxel | Safety: Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
Primary
Safety: Percentage of Participants With Adverse Events Leading to Dose Reduction
Time frame: At time of clinical data cut-off (up to 20 months)
Population: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Trastuzumab Emtansine | Safety: Percentage of Participants With Adverse Events Leading to Dose Reduction | 2.9 percentage of participants |
| Arm B: Trastuzumab + Docetaxel | Safety: Percentage of Participants With Adverse Events Leading to Dose Reduction | 26.7 percentage of participants |
Primary
Safety: Percentage of Participants With Adverse Events Leading to Treatment Interruption
Time frame: At time of clinical data cut-off (up to 20 months)
Population: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Trastuzumab Emtansine | Safety: Percentage of Participants With Adverse Events Leading to Treatment Interruption | 11.8 percentage of participants |
| Arm B: Trastuzumab + Docetaxel | Safety: Percentage of Participants With Adverse Events Leading to Treatment Interruption | 33.3 percentage of participants |
Primary
Safety: Percentage of Participants With Grade 3 and 4 AEs
Grade 3 and 4 AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0. Grade 3 was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living, including bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Grade 4 was defined as life-threatening consequences; urgent intervention indicated.
Time frame: At time of clinical data cut-off (up to 20 months)
Population: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Trastuzumab Emtansine | Safety: Percentage of Participants With Grade 3 and 4 AEs | 20.6 percentage of participants |
| Arm B: Trastuzumab + Docetaxel | Safety: Percentage of Participants With Grade 3 and 4 AEs | 66.7 percentage of participants |
Primary
Safety: Percentage of Participants With Significant Decline in Left Ventricular Ejection Fraction (LVEF)
Significant decline in LVEF was defined as LVEF below 50% and decrease from baseline of 15% points or more. Echocardiogram or multiple-gated acquisition (MUGA) scan was used to assess LVEF.
Time frame: At time of clinical data cut-off (up to 20 months)
Population: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Trastuzumab Emtansine | Safety: Percentage of Participants With Significant Decline in Left Ventricular Ejection Fraction (LVEF) | 0 percentage of participants |
| Arm B: Trastuzumab + Docetaxel | Safety: Percentage of Participants With Significant Decline in Left Ventricular Ejection Fraction (LVEF) | 0 percentage of participants |
Secondary
Duration of Response (DOR)
DOR was defined as the time from the date of initial confirmed PR or CR to the date of disease progression or death within the study. CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the longest diameter of target lesions. Disease progression was defined according to RECIST, v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions.
Time frame: At time of clinical data cut-off (up to 20 months)
Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization. Participants, for whom data were collected, are included in the analysis for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Trastuzumab Emtansine | Duration of Response (DOR) | NA months |
| Arm B: Trastuzumab + Docetaxel | Duration of Response (DOR) | 6.2 months |
Secondary
Immunogenicity: Percentage of Positive Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine
Time frame: Day 1, Cycle 1 (Day 1), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months)
Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization. Only participants with at least one post-dose sample available for ATA analysis were analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Trastuzumab Emtansine | Immunogenicity: Percentage of Positive Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine | 3.0 percentage of participants |
Secondary
Objective Response Rate (ORR)
ORR was defined as percentage of participants with partial response (PR) or complete response (CR) determined on the basis of investigator assessments with the use of RECIST v1.1. Tumor assessments were performed with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis. CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response Rate (OR) = CR + PR.
Time frame: At time of clinical data cut-off (up to 20 months)
Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization. Participants, for whom data were collected, are included in the analysis for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Trastuzumab Emtansine | Objective Response Rate (ORR) | 48.1 percentage of participants |
| Arm B: Trastuzumab + Docetaxel | Objective Response Rate (ORR) | 71.4 percentage of participants |
Secondary
One-Year Survival Rate
One-year survival rate as determined by Kaplan-Meier estimates.
Time frame: At 12 months
Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization. Participants, for whom data were collected, are included in the analysis for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Trastuzumab Emtansine | One-Year Survival Rate | 92.31 percentage of participants |
| Arm B: Trastuzumab + Docetaxel | One-Year Survival Rate | 100.00 percentage of participants |
Secondary
OS Truncated at 2 Years
OS truncated at 2 years was defined as the time from the date of randomization to the date of death from any cause, with deaths occurring beyond 2 years after the participant's randomization date censored at 2 years.
Time frame: At 24 months
Population: Data for this outcome measure were not collected and are therefore not reported. The study was terminated before the time point for data collection of this outcome measure.
Secondary
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death from any cause.
Time frame: At time of clinical data cut-off (up to 20 months)
Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Trastuzumab Emtansine | Overall Survival (OS) | NA months |
| Arm B: Trastuzumab + Docetaxel | Overall Survival (OS) | NA months |
Secondary
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire
The FACT - Taxane is a self-reported instrument which measures the HRQOL of participants receiving taxane containing chemotherapy. The FACT-Taxane consists of 16 items and was designed to assess the impact of taxane treatment-related symptoms from the participant's perspective.
Time frame: Days 1 and 8 of Cycles 1 and 2 and on the first day of each subsequent 21-day cycle thereafter as well as at study drug completion or discontinuation visit (up to 20 months)
Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 1 Day 8 | 27 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 8 Day 1 | 16 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 13 Day 1 | 8 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 9 Day 1 | 15 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 10 Day 1 | 12 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 7 Day 1 | 18 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 11 Day 1 | 11 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 2 Day 8 | 29 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 12 Day 1 | 9 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 14 Day 1 | 7 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 5 Day 1 | 27 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 15 Day 1 | 6 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Study Drug Completion/Discontinuation Visit | 33 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 16 Day 1 | 3 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 4 Day 1 | 30 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 17 Day 1 | 2 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 1 Day 1 | 27 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 18 Day 1 | 2 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 6 Day 1 | 23 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 19 Day 1 | 1 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 3 Day 1 | 33 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 20 Day 1 | 0 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 2 Day 1 | 29 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Study Drug Completion/Discontinuation Visit | 13 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 5 Day 1 | 13 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 9 Day 1 | 10 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 12 Day 1 | 7 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 13 Day 1 | 5 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 20 Day 1 | 1 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 1 Day 1 | 14 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 1 Day 8 | 15 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 2 Day 1 | 15 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 2 Day 8 | 15 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 3 Day 1 | 15 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 4 Day 1 | 14 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 6 Day 1 | 12 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 7 Day 1 | 11 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 8 Day 1 | 11 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 10 Day 1 | 7 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 11 Day 1 | 7 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 14 Day 1 | 5 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 15 Day 1 | 4 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 16 Day 1 | 4 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 17 Day 1 | 2 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 18 Day 1 | 1 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire | Cycle 19 Day 1 | 1 Participants |
Secondary
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire
The FACT-B (version 4) is a self-reported instrument which measures health-related quality of life (HRQOL) of participants with breast cancer.The FACT-B includes the breast cancer sub-scale (BCS) and is comprised of nine items specific to assessing patients' HRQOL in breast cancer.
Time frame: On the first Day of each 21-day Cycle (Day 1, 22, 43, etc.) and at study drug completion or discontinuation visit (up to 20 months)
Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 10 Day 1 | 12 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 4 Day 1 | 30 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 11 Day 1 | 11 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 5 Day 1 | 27 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 12 Day 1 | 9 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 18 Day 1 | 2 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 13 Day 1 | 8 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 6 Day 1 | 23 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 14 Day 1 | 7 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 2 Day 1 | 34 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 15 Day 1 | 6 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 7 Day 1 | 18 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 16 Day 1 | 3 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 19 Day 1 | 1 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 17 Day 1 | 2 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 8 Day 1 | 16 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 3 Day 1 | 33 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 20 Day 1 | 0 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 9 Day 1 | 15 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Study Drug Completion/Discontinuation Visit | 33 Participants |
| Arm A: Trastuzumab Emtansine | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 1 Day 1 | 34 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Study Drug Completion/Discontinuation Visit | 13 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 18 Day 1 | 1 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 1 Day 1 | 15 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 2 Day 1 | 15 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 3 Day 1 | 15 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 5 Day 1 | 13 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 6 Day 1 | 12 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 7 Day 1 | 11 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 8 Day 1 | 11 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 9 Day 1 | 10 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 10 Day 1 | 7 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 11 Day 1 | 7 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 12 Day 1 | 7 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 13 Day 1 | 5 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 14 Day 1 | 5 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 15 Day 1 | 4 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 16 Day 1 | 4 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 17 Day 1 | 2 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 19 Day 1 | 1 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 20 Day 1 | 1 Participants |
| Arm B: Trastuzumab + Docetaxel | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire | Cycle 4 Day 1 | 14 Participants |
Secondary
Pharmacokinetics: Serum Concentrations of Study Medications
Pharmacokinetic (PK) parameters were to be determined in a subset of participants. PK samples from the first 100 Chinese participants were planned to be collected.
Time frame: Day 1, Cycle 1 (Day 1), Day 1, Cycle 2 (Day 22), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months)
Population: No PK analyses were performed as no participants were enrolled from China and no samples were collected.