Breast Cancer
Conditions
Brief summary
This randomized, multicenter, 2-arm, open-label study (TH3RESA) will evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) in comparison with treatment of the physician's choice in participants with metastatic or unresectable locally advanced/recurrent human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Eligible participants will be randomized to receive either trastuzumab emtansine 3.6 mg/kg intravenously every 21 days or treatment of the physician's choice. Participants continue to receive study treatment until disease progression or unacceptable toxicity occurs. This study is also known under Roche study protocol number BO25734.
Interventions
DRUGTrastuzumab emtansine
The dose was calculated based on the patient's Baseline weight on Day 1 of each 3-week treatment cycle. The same dose was administered in subsequent cycles if the patient's weight stayed within 10% of the Baseline weight. If there was a weight change \> 10%, the dose was adjusted accordingly and the recorded weight became the new Baseline weight. Trastuzumab emtansine was provided as a single-use lyophilized formulation.
The treatment of physician's choice (TPC) was a protocol-specified approved or standard of care therapy or combination of therapies, based on frequently used regimens for late-line HER2-positive metastatic breast cancer treatment after receipt of both trastuzumab- and lapatinib-containing regimens. The therapies included single-agent chemotherapy, single-agent (e.g., tamoxifen or aromatase inhibitor) or dual-agent (e.g., aromatase inhibitor with luteinizing hormone releasing hormone \[LHRH\] agonist) hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy. Participants who had documented progressive disease (PD) were eligible to switch treatment to receive trastuzumab emtansine 3.6 mg/kg. Participants who switched treatment remained on trastuzumab emtansine treatment until another PD event or unmanageable toxicity. The formulation, storage, and preparation of all TPC were as per the appropriate package insert or national prescribing information.
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
* Adult participants ≥ 18 years of age. * Histologically or cytologically documented breast cancer. * Metastatic or unresectable locally advanced/recurrent breast cancer. * HER2-positive disease by prospective laboratory confirmation. * Disease progression on the last regimen received as defined by the investigator. * Prior treatment with an trastuzumab, a taxane, and lapatinib. * Disease progression after at least two regimens of HER2-directed therapy in the metastatic or unresectable locally advanced/recurrent setting. * Adequate organ function, as evidenced by laboratory results. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. * Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or multi gated acquisition scan.
Exclusion criteria
* Chemotherapy ≤ 21 days before first study treatment. * Trastuzumab ≤ 21 days before first study treatment. * Lapatinib ≤ 14 days before first study treatment. * Prior enrollment in a trastuzumab emtansine containing study, regardless whether the patient received prior trastuzumab emtansine. * Brain metastases that are untreated or symptomatic, or require any radiation, surgery or corticosteroid therapy to control symptoms within 1 month of randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) | Progression-free survival was defined as the time from randomization to the first documented disease progression by investigator assessment using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurred first. Progression-free survival was a co-primary endpoint. |
| Overall Survival | Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) | Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was a co-primary endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6-month and 1-year Survival | Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) | 6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively, as estimated using Kaplan-Meier method. |
| Time to Pain Symptom Progression | Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) | Time to pain symptom progression was defined as the time from randomization to the first documentation of an increase in narcotic use and/or a 10 point increase from Baseline in the pain score as measured by the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire for patients with bone metastases (EORTC QLQ-BM22). The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain. |
| Percentage of Participants With an Objective Response | Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) | An objective response was defined as a complete or partial response determined on 2 consecutive occasions ≥ 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be \< 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. Participants who had no post-baseline tumor assessment were counted as non-responders. |
| Overall Survival (Final Analysis) | Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years) | Overall survival was defined as the time from randomization to death from any cause. |
| 6-month and 1-year Survival (Final Analysis) | Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years) | 6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively, as estimated using Kaplan-Meier method. |
| Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) | The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain. A negative change score indicates improvement. |
| Duration of the Objective Response | Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) | Duration of the objective response was defined as the time from the first tumor assessment that was judged to indicate that the patient had an objective response to the time of first documented disease progression using RECIST v1.1 per investigator assessment or death from any cause, whichever occurred first. |
Countries
Australia, Belgium, Brazil, Canada, Czechia, France, Germany, Hungary, India, Israel, Italy, Norway, Poland, Russia, Slovakia, South Korea, Spain, Sweden, Switzerland, Thailand, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 602 patients were randomized to the study (404 to receive Trastuzumab Emtansine and 198 to receive Treatment of Physician's Choice).
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab Emtansine Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity. | 404 |
| Treatment of Physician's Choice Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy. | 198 |
| Total | 602 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 247 | 122 |
| Overall Study | Lost to Follow-up | 14 | 4 |
| Overall Study | Non-compliance | 3 | 1 |
| Overall Study | Physician Decision | 4 | 4 |
| Overall Study | Reason Not Specified | 0 | 1 |
| Overall Study | Study Completed by Sponsor | 103 | 34 |
| Overall Study | Withdrawal by Subject | 33 | 32 |
Baseline characteristics
| Characteristic | Trastuzumab Emtansine | Treatment of Physician's Choice | Total |
|---|---|---|---|
| Age, Continuous | 53.3 years STANDARD_DEVIATION 10.4 | 54.3 years STANDARD_DEVIATION 10.8 | 53.6 years STANDARD_DEVIATION 10.5 |
| Sex: Female, Male Female | 401 Participants | 197 Participants | 598 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 371 / 403 | 148 / 184 | 74 / 94 |
| serious Total, serious adverse events | 102 / 403 | 41 / 184 | 19 / 94 |
Outcome results
Primary
Overall Survival
Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was a co-primary endpoint.
Time frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Population: Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Emtansine | Overall Survival | NA Months |
| Treatment of Physician's Choice | Overall Survival | 14.9 Months |
Comparison: The analysis was stratified for 1) World region (United States, Western Europe, or Other); 2) Number of prior regimens, excluding single-agent hormones, for treatment of metastatic or unresectable locally advanced/recurrent disease (≤ 3 or \> 3); and 3) Presence of visceral disease (any visceral disease vs no visceral disease).p-value: 0.003495% CI: [0.369, 0.826]Log Rank
Primary
Progression-free Survival
Progression-free survival was defined as the time from randomization to the first documented disease progression by investigator assessment using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurred first. Progression-free survival was a co-primary endpoint.
Time frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Population: Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Emtansine | Progression-free Survival | 6.2 Months |
| Treatment of Physician's Choice | Progression-free Survival | 3.3 Months |
Comparison: The analysis was stratified for 1) World region (United States, Western Europe, or Other); 2) Number of prior regimens, excluding single-agent hormones, for treatment of metastatic or unresectable locally advanced/recurrent disease (≤ 3 or \> 3); and 3) Presence of visceral disease (any visceral disease vs no visceral disease).p-value: <0.000195% CI: [0.422, 0.661]Log Rank
Secondary
6-month and 1-year Survival
6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively, as estimated using Kaplan-Meier method.
Time frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Population: Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab Emtansine | 6-month and 1-year Survival | 6-Month Survival | 90.9 Percentage of participants |
| Trastuzumab Emtansine | 6-month and 1-year Survival | 1-Year Survival | 68.6 Percentage of participants |
| Treatment of Physician's Choice | 6-month and 1-year Survival | 6-Month Survival | 78.3 Percentage of participants |
| Treatment of Physician's Choice | 6-month and 1-year Survival | 1-Year Survival | 56.9 Percentage of participants |
Comparison: 6-month survivalp-value: 0.001195% CI: [5.03, 20.09]z-test
Comparison: 1-year survivalp-value: 0.180595% CI: [-5.41, 28.75]z-test
Secondary
6-month and 1-year Survival (Final Analysis)
6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively, as estimated using Kaplan-Meier method.
Time frame: Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
Population: Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab Emtansine | 6-month and 1-year Survival (Final Analysis) | 6-Month Survival | 91.3 Percentage of participants |
| Trastuzumab Emtansine | 6-month and 1-year Survival (Final Analysis) | 1-Year Survival | 76.5 Percentage of participants |
| Treatment of Physician's Choice | 6-month and 1-year Survival (Final Analysis) | 6-Month Survival | 78.9 Percentage of participants |
| Treatment of Physician's Choice | 6-month and 1-year Survival (Final Analysis) | 1-Year Survival | 65.6 Percentage of participants |
Comparison: 6-month survivalp-value: 0.000395% CI: [5.67, 19.14]z-test
Comparison: 1-year survivalp-value: 0.010495% CI: [2.58, 19.33]z-test
Secondary
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle
The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain. A negative change score indicates improvement.
Time frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Population: Randomized population: All participants who were randomized to the study. Only participants with a Baseline pain score and at least 1 post-baseline pain score were included in the analysis. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 21 (n=3,0) | -3.7 Units on a scale | Standard Deviation 6.4 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 3 (n=257,86) | -4.6 Units on a scale | Standard Deviation 21.1 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 6 (n=195,42) | -4.8 Units on a scale | Standard Deviation 23.5 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 7 (n=163,30) | -4.2 Units on a scale | Standard Deviation 23.8 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 8 (n=130,20) | -7.0 Units on a scale | Standard Deviation 21 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 9 (n=97,15) | -5.8 Units on a scale | Standard Deviation 22.2 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 10 (n=80,7) | -8.9 Units on a scale | Standard Deviation 21.2 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 11 (n=56,8) | -10.5 Units on a scale | Standard Deviation 23.1 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 12 (n=48,7) | -11.3 Units on a scale | Standard Deviation 25.8 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 13 (n=40,5) | -10.0 Units on a scale | Standard Deviation 23.3 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 14 (n=33,5) | -10.1 Units on a scale | Standard Deviation 21.8 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 15 (n=27,3) | -13.2 Units on a scale | Standard Deviation 22 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 20 (n=4,0) | -5.6 Units on a scale | Standard Deviation 23.1 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Termination Visit (n=84,37) | -1.6 Units on a scale | Standard Deviation 21.8 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 4 (n=236,74) | -4.8 Units on a scale | Standard Deviation 19.6 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 5 (n=224,54) | -6.6 Units on a scale | Standard Deviation 22.8 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 16 (n=19,3) | -12.3 Units on a scale | Standard Deviation 19.6 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 17 (n=15,2) | -7.4 Units on a scale | Standard Deviation 22.9 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 18 (n=11,0) | -9.1 Units on a scale | Standard Deviation 12 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 19 (n=8,0) | 1.4 Units on a scale | Standard Deviation 9.3 |
| Trastuzumab Emtansine | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 2 (n=282,98) | -3.4 Units on a scale | Standard Deviation 21.1 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 16 (n=19,3) | -3.7 Units on a scale | Standard Deviation 6.4 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 2 (n=282,98) | -9.4 Units on a scale | Standard Deviation 22.1 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 14 (n=33,5) | 0.0 Units on a scale | Standard Deviation 7.9 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 3 (n=257,86) | -6.1 Units on a scale | Standard Deviation 21.4 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 4 (n=236,74) | -3.8 Units on a scale | Standard Deviation 24.1 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 5 (n=224,54) | -2.7 Units on a scale | Standard Deviation 18.9 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 18 (n=11,0) | NA Units on a scale | — |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 6 (n=195,42) | 2.4 Units on a scale | Standard Deviation 17.1 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 15 (n=27,3) | 0.0 Units on a scale | Standard Deviation 0 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 7 (n=163,30) | -1.5 Units on a scale | Standard Deviation 15.6 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 19 (n=8,0) | NA Units on a scale | — |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 8 (n=130,20) | 2.2 Units on a scale | Standard Deviation 18.6 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 12 (n=48,7) | 1.6 Units on a scale | Standard Deviation 7.7 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 9 (n=97,15) | 6.7 Units on a scale | Standard Deviation 20.1 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 20 (n=4,0) | NA Units on a scale | — |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 10 (n=80,7) | 1.6 Units on a scale | Standard Deviation 11.9 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 21 (n=3,0) | NA Units on a scale | — |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 11 (n=56,8) | 0.0 Units on a scale | Standard Deviation 8.4 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 17 (n=15,2) | -5.6 Units on a scale | Standard Deviation 7.9 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Termination Visit (n=84,37) | -9.0 Units on a scale | Standard Deviation 23.3 |
| Treatment of Physician's Choice | Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle | Cycle 13 (n=40,5) | 2.2 Units on a scale | Standard Deviation 12.2 |
Secondary
Duration of the Objective Response
Duration of the objective response was defined as the time from the first tumor assessment that was judged to indicate that the patient had an objective response to the time of first documented disease progression using RECIST v1.1 per investigator assessment or death from any cause, whichever occurred first.
Time frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Population: Randomized population: All participants who were randomized to the study. Only participants with an objective response were included in the analysis. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Emtansine | Duration of the Objective Response | 9.7 Months |
| Treatment of Physician's Choice | Duration of the Objective Response | NA Months |
Secondary
Overall Survival (Final Analysis)
Overall survival was defined as the time from randomization to death from any cause.
Time frame: Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
Population: Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Emtansine | Overall Survival (Final Analysis) | 22.7 Months |
| Treatment of Physician's Choice | Overall Survival (Final Analysis) | 15.8 Months |
Comparison: The analysis was stratified for 1) World region (United States, Western Europe, or Other); 2) Number of prior regimens, excluding single-agent hormones, for treatment of metastatic or unresectable locally advanced/recurrent disease (≤ 3 or \> 3); and 3) Presence of visceral disease (any visceral disease versus no visceral disease).p-value: 0.000795% CI: [0.539, 0.85]Log Rank
Secondary
Percentage of Participants With an Objective Response
An objective response was defined as a complete or partial response determined on 2 consecutive occasions ≥ 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be \< 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. Participants who had no post-baseline tumor assessment were counted as non-responders.
Time frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Population: Randomized population: All participants who were randomized to the study. Only participants with measurable disease at Baseline were included in the analysis. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Emtansine | Percentage of Participants With an Objective Response | 31.3 Percentage of participants |
| Treatment of Physician's Choice | Percentage of Participants With an Objective Response | 8.6 Percentage of participants |
Comparison: The analysis was stratified for 1) World region (United States, Western Europe, or Other); 2) Number of prior regimens, excluding single-agent hormones, for treatment of metastatic or unresectable locally advanced/recurrent disease (≤ 3 or \> 3); and 3) Presence of visceral disease (any visceral disease vs no visceral disease).p-value: <0.000195% CI: [16.2, 29.2]Mantel Haenszel
Secondary
Time to Pain Symptom Progression
Time to pain symptom progression was defined as the time from randomization to the first documentation of an increase in narcotic use and/or a 10 point increase from Baseline in the pain score as measured by the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire for patients with bone metastases (EORTC QLQ-BM22). The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain.
Time frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Population: Randomized population: All participants who were randomized to the study. Only participants with a Baseline pain score and at least 1 post-baseline pain score were included in the analysis. Participants were included in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Emtansine | Time to Pain Symptom Progression | 2.9 Months |
| Treatment of Physician's Choice | Time to Pain Symptom Progression | 3.6 Months |
Comparison: The analysis was stratified for 1) World region (United States, Western Europe, or Other); 2) Number of prior regimens, excluding single-agent hormones, for treatment of metastatic or unresectable locally advanced/recurrent disease (≤ 3 or \> 3); and 3) Presence of visceral disease (any visceral disease vs no visceral disease).p-value: 0.495295% CI: [0.819, 1.517]Log Rank