Breast Cancer
Conditions
Brief summary
This study will evaluate the efficacy and safety of Perjeta (pertuzumab) in combination with Herceptin (trastuzumab) in participants with metastatic breast cancer who have progressed on trastuzumab-based therapy (Cohorts 1 and 2), and will make a preliminary assessment of the efficacy and safety of single-agent pertuzumab (Cohort 3). Objective response rate and clinical benefit will be assessed. Pertuzumab will be administered at an initial dose of 840 milligrams (mg) intravenously (IV) on Day 1, followed by 420 mg IV every 3 weeks. Trastuzumab will be administered at the same schedule the participant was following before entry into the study. An additional cohort of participants at certain centers will receive pertuzumab monotherapy at an initial dose of 840 mg IV on Day 1, followed by 420 mg IV every 3 weeks. These participants may have trastuzumab added to the regimen in the event of progression during single-agent pertuzumab treatment.
Interventions
DRUGPertuzumab
Loading dose 840 mg IV on Day 2 of Cycle 1, followed by 420 mg every 3 weeks thereafter, until disease progression or unacceptable toxicity.
DRUGTrastuzumab
2 mg/kg IV once weekly, or as 6 mg/kg every 3 weeks, beginning on Day 1 of Cycle 1 and on Day 1 of each 3-week cycle thereafter until disease progression or unacceptable toxicity.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Females greater than or equal to (≥) 18 years of age, with histologically-confirmed HER2-positive breast cancer * Metastatic breast cancer, with progression on trastuzumab-based therapy as last treatment for metastatic disease * Less than or equal to (≤) 3 chemotherapy regimens prior to study entry * Last trastuzumab dose ≤9 weeks before study entry for participants receiving pertuzumab + trastuzumab, and ≥4 weeks for participants receiving pertuzumab monotherapy * Left ventricular ejection fraction ≥55% at study entry
Exclusion criteria
* Previous treatment with an anti-cancer vaccine or any targeted therapy other than trastuzumab * Brain metastases * History of any cardiac adverse event related to trastuzumab therapy * Any other malignancy in the last 5 years, except for basal cell cancer or cancer in situ of the cervix
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1 and 2: Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 During Dual-Agent Treatment | Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression) | Tumor response was assessed using RECIST version 1.0 to determine the objective response (OR) rate, or the percentage of participants with either confirmed CR or PR. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameter compared to Baseline. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The OR rate was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100. |
| Cohorts 1 and 2: Percentage of Participants With a Confirmed Best Overall Response of CR, PR, or Stable Disease (SD) According to RECIST Version 1.0 During Dual-Agent Treatment | Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression) | Tumor response was assessed using RECIST version 1.0 to determine the clinical benefit response (CBR) rate, or the percentage of participants with either confirmed CR or PR, or SD lasting at least 6 months. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The CBR rate was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1 and 2: Duration of Response According to RECIST Version 1.0 | Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression) | Tumor response was assessed using RECIST version 1.0 to determine OR and CBR rates. Duration of OR was defined as time from initial response of CR or PR to time of disease progression or death. Duration of CBR was defined similarly as time from initial response of CR or PR, or SD lasting at least 6 months, to time of disease progression or death. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. Participants without progression or death following confirmed CR or PR were censored at the last tumor assessment. Duration of response was estimated using Kaplan-Meier analysis and expressed in weeks. |
| Cohorts 1 and 2: Time to Objective Response According to RECIST Version 1.0 | Up to approximately 21 months (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression; final analysis using February 2008 cutoff date) | Tumor response was assessed using RECIST version 1.0 to determine the OR rate. Time to response was defined as the time from first dose to the time of initial response of CR or PR. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. Participants with disease progression were censored at the time of progression, and those with neither disease progression nor OR were censored at the last tumor assessment. Time to response was estimated using Kaplan-Meier analysis and expressed in weeks. |
| Cohorts 1 and 2: Percentage of Participants With Disease Progression According to RECIST Version 1.0 | Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression) | Tumor response was assessed using RECIST version 1.0 to assess for disease progression, defined as at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions. The percentage of participants with disease progression was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100. |
| Cohort 3: Percentage of Participants With a Confirmed Best Overall Response of CR or PR According to RECIST Version 1.0 During Single-Agent Treatment With Pertuzumab | Up to approximately 7.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression) | Tumor response was assessed using RECIST version 1.0 to determine the OR rate, or the percentage of participants with either confirmed CR or PR. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The OR rate was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100. |
| Cohorts 1 and 2: Progression-Free Survival (PFS) According to RECIST Version 1.0 | Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression) | Tumor response was assessed using RECIST version 1.0 to assess for disease progression, defined as at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions. PFS was defined as the time from first dose to the time of disease progression or death. Participants without progression or death were censored at the last tumor assessment. PFS was estimated using Kaplan-Meier analysis and expressed in weeks. |
| Cohorts 1 and 2: Percentage of Participants Who Died | Up to approximately 4.5 years (during treatment; then every 4 months until death, withdrawn consent, loss to follow-up, or 3 years after last dose; final analysis using November 2010 cutoff date) | Participants were followed for survival data during and after treatment for a maximum of 3 years after the last dose until death, withdrawal of consent, or loss to follow-up. The percentage of participants who died was calculated as \[number of participants with event divided by the number analyzed\] multiplied by 100. |
| Cohorts 1 and 2: Overall Survival (OS) | Up to approximately 4.5 years (during treatment; then every 4 months until death, withdrawn consent, loss to follow-up, or 3 years after last dose; final analysis using November 2010 cutoff date) | Participants were followed for survival data during and after treatment for a maximum of 3 years after the last dose until death, withdrawal of consent, or loss to follow-up. OS was defined as the time from first dose to the time of death from any cause. Participants who did not experience death were censored at the last known alive date. OS was estimated using Kaplan-Meier and expressed in months. |
| Cohorts 1 and 2: Time to Progression (TTP) According to RECIST Version 1.0 | Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression) | Tumor response was assessed using RECIST version 1.0 to assess for disease progression, defined as at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions. TTP was defined as the time from first dose to the time of first documented disease progression. Participants who withdrew from the study without documented progression were censored at the last tumor assessment. TTP was estimated using Kaplan-Meier analysis and expressed in weeks. |
| Cohort 3: Percentage of Participants With a Confirmed Best Overall Response of CR, PR, or SD According to RECIST Version 1.0 During Single-Agent Treatment With Pertuzumab | Up to approximately 7.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression) | Tumor response was assessed using RECIST version 1.0 to determine the CBR rate, or the percentage of participants with either confirmed CR or PR, or SD lasting at least 6 months. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The CBR rate was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100. |
Countries
Canada, France, Italy, Spain, United Kingdom
Participant flow
Pre-assignment details
A total of 99 participants with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer were screened for Cohorts 1 and 2, of whom 66 were recruited. Following primary analysis of Cohorts 1 and 2, a total of 51 new participants were screened for Cohort 3, of whom 29 were recruited.
Participants by arm
| Arm | Count |
|---|---|
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) Females with HER2-positive metastatic breast cancer received dual-agent treatment with pertuzumab and trastuzumab. Recruitment for Cohorts 1 and 2 was conducted separately; however, the same regimen was administered to both sets of participants. Trastuzumab was administered via IV infusion as 2 mg/kg once weekly, or as 6 mg/kg every 3 weeks, beginning on Day 1 of Cycle 1. Pertuzumab was administered via IV infusion at a loading dose of 840 mg followed by a standard dose of 420 mg every 3 weeks, beginning on Day 2 of Cycle 1. Thereafter, both medications were administered on Day 1 of each 3-week cycle. Treatment continued for a minimum of 8 cycles and could be extended until disease progression, intolerable toxicity, or death. | 66 |
| Pertuzumab +/- Trastuzumab (Cohort 3) Females with HER2-positive metastatic breast cancer received single-agent treatment with pertuzumab. Recruitment for Cohort 3 was conducted following primary analysis of Cohorts 1 and 2. Pertuzumab was administered via IV infusion at a loading dose of 840 mg followed by a standard dose of 420 mg every 3 weeks, administered on Day 1 of each 3-week cycle. Participants with documented disease progression could have trastuzumab added to the regimen, per the dosing schedule described for Cohorts 1 and 2, to receive dual-agent treatment until disease progression, intolerable toxicity, or death. | 29 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Insufficient Therapeutic Response | 56 | 26 |
| Overall Study | Other | 8 | 1 |
| Overall Study | Programming Error | 1 | 0 |
Baseline characteristics
| Characteristic | Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Pertuzumab +/- Trastuzumab (Cohort 3) | Total |
|---|---|---|---|
| Age, Continuous | 54.9 years STANDARD_DEVIATION 12.6 | 53.0 years STANDARD_DEVIATION 7.95 | 54.3 years STANDARD_DEVIATION 11.37 |
| Sex: Female, Male Female | 66 Participants | 29 Participants | 95 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 | 62 / 66 | 28 / 29 |
| serious Total, serious adverse events | 12 / 66 | 1 / 29 |
Outcome results
Primary
Cohorts 1 and 2: Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 During Dual-Agent Treatment
Tumor response was assessed using RECIST version 1.0 to determine the objective response (OR) rate, or the percentage of participants with either confirmed CR or PR. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameter compared to Baseline. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The OR rate was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.
Time frame: Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Population: All Treated Population (Cohorts 1 and 2 only).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Cohorts 1 and 2: Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 During Dual-Agent Treatment | 24.2 percentage of participants |
Primary
Cohorts 1 and 2: Percentage of Participants With a Confirmed Best Overall Response of CR, PR, or Stable Disease (SD) According to RECIST Version 1.0 During Dual-Agent Treatment
Tumor response was assessed using RECIST version 1.0 to determine the clinical benefit response (CBR) rate, or the percentage of participants with either confirmed CR or PR, or SD lasting at least 6 months. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The CBR rate was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.
Time frame: Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Population: All Treated Population (Cohorts 1 and 2 only).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Cohorts 1 and 2: Percentage of Participants With a Confirmed Best Overall Response of CR, PR, or Stable Disease (SD) According to RECIST Version 1.0 During Dual-Agent Treatment | 50.0 percentage of participants |
Secondary
Cohort 3: Percentage of Participants With a Confirmed Best Overall Response of CR or PR According to RECIST Version 1.0 During Single-Agent Treatment With Pertuzumab
Tumor response was assessed using RECIST version 1.0 to determine the OR rate, or the percentage of participants with either confirmed CR or PR. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The OR rate was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.
Time frame: Up to approximately 7.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Population: All Treated Population (Cohort 3 only).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Cohort 3: Percentage of Participants With a Confirmed Best Overall Response of CR or PR According to RECIST Version 1.0 During Single-Agent Treatment With Pertuzumab | 3.4 percentage of participants |
Secondary
Cohort 3: Percentage of Participants With a Confirmed Best Overall Response of CR, PR, or SD According to RECIST Version 1.0 During Single-Agent Treatment With Pertuzumab
Tumor response was assessed using RECIST version 1.0 to determine the CBR rate, or the percentage of participants with either confirmed CR or PR, or SD lasting at least 6 months. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The CBR rate was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.
Time frame: Up to approximately 7.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Population: All Treated Population (Cohort 3 only).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Cohort 3: Percentage of Participants With a Confirmed Best Overall Response of CR, PR, or SD According to RECIST Version 1.0 During Single-Agent Treatment With Pertuzumab | 10.3 percentage of participants |
Secondary
Cohorts 1 and 2: Duration of Response According to RECIST Version 1.0
Tumor response was assessed using RECIST version 1.0 to determine OR and CBR rates. Duration of OR was defined as time from initial response of CR or PR to time of disease progression or death. Duration of CBR was defined similarly as time from initial response of CR or PR, or SD lasting at least 6 months, to time of disease progression or death. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. Participants without progression or death following confirmed CR or PR were censored at the last tumor assessment. Duration of response was estimated using Kaplan-Meier analysis and expressed in weeks.
Time frame: Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Population: All Treated Population (Cohorts 1 and 2 only).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Cohorts 1 and 2: Duration of Response According to RECIST Version 1.0 | Objective response | 40.1 weeks |
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Cohorts 1 and 2: Duration of Response According to RECIST Version 1.0 | Clinical benefit response | 50.14 weeks |
Secondary
Cohorts 1 and 2: Overall Survival (OS)
Participants were followed for survival data during and after treatment for a maximum of 3 years after the last dose until death, withdrawal of consent, or loss to follow-up. OS was defined as the time from first dose to the time of death from any cause. Participants who did not experience death were censored at the last known alive date. OS was estimated using Kaplan-Meier and expressed in months.
Time frame: Up to approximately 4.5 years (during treatment; then every 4 months until death, withdrawn consent, loss to follow-up, or 3 years after last dose; final analysis using November 2010 cutoff date)
Population: All Treated Population (Cohorts 1 and 2 only).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Cohorts 1 and 2: Overall Survival (OS) | 38.5 months |
Secondary
Cohorts 1 and 2: Percentage of Participants Who Died
Participants were followed for survival data during and after treatment for a maximum of 3 years after the last dose until death, withdrawal of consent, or loss to follow-up. The percentage of participants who died was calculated as \[number of participants with event divided by the number analyzed\] multiplied by 100.
Time frame: Up to approximately 4.5 years (during treatment; then every 4 months until death, withdrawn consent, loss to follow-up, or 3 years after last dose; final analysis using November 2010 cutoff date)
Population: All Treated Population (Cohorts 1 and 2 only).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Cohorts 1 and 2: Percentage of Participants Who Died | 30.3 percentage of participants |
Secondary
Cohorts 1 and 2: Percentage of Participants With Disease Progression According to RECIST Version 1.0
Tumor response was assessed using RECIST version 1.0 to assess for disease progression, defined as at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions. The percentage of participants with disease progression was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.
Time frame: Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Population: All Treated Population (Cohorts 1 and 2 only).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Cohorts 1 and 2: Percentage of Participants With Disease Progression According to RECIST Version 1.0 | 93.9 percentage of participants |
Secondary
Cohorts 1 and 2: Progression-Free Survival (PFS) According to RECIST Version 1.0
Tumor response was assessed using RECIST version 1.0 to assess for disease progression, defined as at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions. PFS was defined as the time from first dose to the time of disease progression or death. Participants without progression or death were censored at the last tumor assessment. PFS was estimated using Kaplan-Meier analysis and expressed in weeks.
Time frame: Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Population: All Treated Population (Cohorts 1 and 2 only).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Cohorts 1 and 2: Progression-Free Survival (PFS) According to RECIST Version 1.0 | 24.0 weeks |
Secondary
Cohorts 1 and 2: Time to Objective Response According to RECIST Version 1.0
Tumor response was assessed using RECIST version 1.0 to determine the OR rate. Time to response was defined as the time from first dose to the time of initial response of CR or PR. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. Participants with disease progression were censored at the time of progression, and those with neither disease progression nor OR were censored at the last tumor assessment. Time to response was estimated using Kaplan-Meier analysis and expressed in weeks.
Time frame: Up to approximately 21 months (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression; final analysis using February 2008 cutoff date)
Population: All Treated Population (Cohorts 1 and 2 only).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Cohorts 1 and 2: Time to Objective Response According to RECIST Version 1.0 | 11.14 weeks |
Secondary
Cohorts 1 and 2: Time to Progression (TTP) According to RECIST Version 1.0
Tumor response was assessed using RECIST version 1.0 to assess for disease progression, defined as at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions. TTP was defined as the time from first dose to the time of first documented disease progression. Participants who withdrew from the study without documented progression were censored at the last tumor assessment. TTP was estimated using Kaplan-Meier analysis and expressed in weeks.
Time frame: Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)
Population: All Treated Population (Cohorts 1 and 2 only).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Cohorts 1 and 2: Time to Progression (TTP) According to RECIST Version 1.0 | 23.2 weeks |