A Study of Perjeta (Pertuzumab) in Combination With Herceptin (Trastuzumab) in Participants With Metastatic Breast Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pertuzumab + Trastuzumab (Cohorts 1 and 2) Females with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer will receive dual-agent treatment with pertuzumab and trastuzumab. Trastuzumab will be administered IV as 2 milligrams per kilogram (mg/kg) once weekly, or as 6 mg/kg every 3 weeks, beginning on Day 1 of Cycle 1. Pertuzumab will be administered IV 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 will be administered on Day 1 of each 3-week cycle. Treatment will continue for a minimum of 8 cycles and may be extended until disease progression, intolerable toxicity, or death. |
Drug: Pertuzumab
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.
Other Names:
Drug: Trastuzumab
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.
Other Names:
|
| Experimental: Pertuzumab +/- Trastuzumab (Cohort 3) Females with HER2-positive metastatic breast cancer will receive single-agent treatment with pertuzumab. Pertuzumab will be administered IV 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 may 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. |
Drug: Pertuzumab
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.
Other Names:
Drug: Trastuzumab
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Edmonton | Alberta | Canada | T6G 1Z2 | |
| 2 | Vancouver | British Columbia | Canada | V5Z 4E6 | |
| 3 | London | Ontario | Canada | N6A 4L6 | |
| 4 | Ottawa | Ontario | Canada | K1H 8L6 | |
| 5 | Toronto | Ontario | Canada | M4N 3M5 | |
| 6 | Besancon | France | 25030 | ||
| 7 | Dijon | France | 21079 | ||
| 8 | Lille | France | 59020 | ||
| 9 | Montpellier | France | 34298 | ||
| 10 | Modena | Emilia-Romagna | Italy | 41100 | |
| 11 | Parma | Emilia-Romagna | Italy | 43100 | |
| 12 | Milano | Lombardia | Italy | 20133 | |
| 13 | Barcelona | Spain | 08003 | ||
| 14 | Barcelona | Spain | 08035 | ||
| 15 | Valencia | Spain | 46009 | ||
| 16 | Valencia | Spain | 46010 | ||
| 17 | Edinburgh | United Kingdom | EH4 2XU | ||
| 18 | Manchester | United Kingdom | M20 4BX | ||
| 19 | Northwood | United Kingdom | HA6 2RN | ||
| 20 | Truro | United Kingdom | TR1 3LJ |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Chair: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BO17929
- 2005-003493-19
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Pertuzumab +/- Trastuzumab (Cohort 3) |
|---|---|---|
| Arm/Group Description | 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 intravenous (IV) infusion as 2 milligrams per kilogram (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 milligrams (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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 66 | 29 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 66 | 29 |
Baseline Characteristics
| Arm/Group Title | Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Pertuzumab +/- Trastuzumab (Cohort 3) | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | Total of all reporting groups |
| Overall Participants | 66 | 29 | 95 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
54.9
(12.60)
|
53.0
(7.95)
|
54.3
(11.37)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
66
100%
|
29
100%
|
95
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | 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 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Treated Population (Cohorts 1 and 2 only). |
| Arm/Group Title | Pertuzumab + Trastuzumab (Cohorts 1 and 2) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 66 |
| Number (80% Confidence Interval) [percentage of participants] |
24.2
36.7%
|
| Title | 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 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Treated Population (Cohorts 1 and 2 only). |
| Arm/Group Title | Pertuzumab + Trastuzumab (Cohorts 1 and 2) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 66 |
| Number (80% Confidence Interval) [percentage of participants] |
50.0
75.8%
|
| Title | 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 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Treated Population (Cohort 3 only). |
| Arm/Group Title | Pertuzumab (Cohort 3) |
|---|---|
| Arm/Group Description | 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. The treatment regimen was maintained until disease progression, intolerable toxicity, death, and/or transition to dual-agent therapy with trastuzumab. |
| Measure Participants | 29 |
| Number (80% Confidence Interval) [percentage of participants] |
3.4
5.2%
|
| Title | 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 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Treated Population (Cohort 3 only). |
| Arm/Group Title | Pertuzumab (Cohort 3) |
|---|---|
| Arm/Group Description | 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. The treatment regimen was maintained until disease progression, intolerable toxicity, death, and/or transition to dual-agent therapy with trastuzumab. |
| Measure Participants | 29 |
| Number (80% Confidence Interval) [percentage of participants] |
10.3
15.6%
|
| Title | Cohorts 1 and 2: Duration of Response According to RECIST Version 1.0 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Treated Population (Cohorts 1 and 2 only). |
| Arm/Group Title | Pertuzumab + Trastuzumab (Cohorts 1 and 2) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 66 |
| Objective response |
40.1
|
| Clinical benefit response |
50.14
|
| Title | Cohorts 1 and 2: Time to Objective Response According to RECIST Version 1.0 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Treated Population (Cohorts 1 and 2 only). |
| Arm/Group Title | Pertuzumab + Trastuzumab (Cohorts 1 and 2) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 66 |
| Median (Full Range) [weeks] |
11.14
|
| Title | Cohorts 1 and 2: Percentage of Participants With Disease Progression According to RECIST Version 1.0 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Treated Population (Cohorts 1 and 2 only). |
| Arm/Group Title | Pertuzumab + Trastuzumab (Cohorts 1 and 2) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 66 |
| Number [percentage of participants] |
93.9
142.3%
|
| Title | Cohorts 1 and 2: Time to Progression (TTP) According to RECIST Version 1.0 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Treated Population (Cohorts 1 and 2 only). |
| Arm/Group Title | Pertuzumab + Trastuzumab (Cohorts 1 and 2) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 66 |
| Median (Full Range) [weeks] |
23.2
|
| Title | Cohorts 1 and 2: Progression-Free Survival (PFS) According to RECIST Version 1.0 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Treated Population (Cohorts 1 and 2 only). |
| Arm/Group Title | Pertuzumab + Trastuzumab (Cohorts 1 and 2) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 66 |
| Median (80% Confidence Interval) [weeks] |
24.0
|
| Title | Cohorts 1 and 2: Percentage of Participants Who Died |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Treated Population (Cohorts 1 and 2 only). |
| Arm/Group Title | Pertuzumab + Trastuzumab (Cohorts 1 and 2) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 66 |
| Number [percentage of participants] |
30.3
45.9%
|
| Title | Cohorts 1 and 2: Overall Survival (OS) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Treated Population (Cohorts 1 and 2 only). |
| Arm/Group Title | Pertuzumab + Trastuzumab (Cohorts 1 and 2) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 66 |
| Median (80% Confidence Interval) [months] |
38.5
|
Adverse Events
| Time Frame | Up to approximately 9.5 years (from Day 1 until treatment discontinuation) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Analysis Population Description: All Treated Population. | |||
| Arm/Group Title | Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Pertuzumab +/- Trastuzumab (Cohort 3) | ||
| Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Pertuzumab +/- Trastuzumab (Cohort 3) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Pertuzumab +/- Trastuzumab (Cohort 3) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/66 (18.2%) | 1/29 (3.4%) | ||
| Cardiac disorders | ||||
| Palpitations | 1/66 (1.5%) | 0/29 (0%) | ||
| Gastrointestinal disorders | ||||
| Haematemesis | 1/66 (1.5%) | 0/29 (0%) | ||
| General disorders | ||||
| Performance status decreased | 1/66 (1.5%) | 0/29 (0%) | ||
| Hepatobiliary disorders | ||||
| Hepatic failure | 1/66 (1.5%) | 0/29 (0%) | ||
| Infections and infestations | ||||
| Cellulitis | 1/66 (1.5%) | 0/29 (0%) | ||
| Device related infection | 1/66 (1.5%) | 0/29 (0%) | ||
| Pneumonia | 1/66 (1.5%) | 0/29 (0%) | ||
| Pneumonia pneumococcal | 1/66 (1.5%) | 0/29 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Femur fracture | 0/66 (0%) | 1/29 (3.4%) | ||
| Metabolism and nutrition disorders | ||||
| Hypokalaemia | 1/66 (1.5%) | 0/29 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 2/66 (3%) | 0/29 (0%) | ||
| Nervous system disorders | ||||
| Osmotic demyelination syndrome | 0/66 (0%) | 1/29 (3.4%) | ||
| Loss of consciousness | 1/66 (1.5%) | 0/29 (0%) | ||
| Dizziness | 1/66 (1.5%) | 0/29 (0%) | ||
| Psychiatric disorders | ||||
| Paranoia | 1/66 (1.5%) | 0/29 (0%) | ||
| Surgical and medical procedures | ||||
| Toe amputation | 1/66 (1.5%) | 0/29 (0%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 1/66 (1.5%) | 0/29 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Pertuzumab + Trastuzumab (Cohorts 1 and 2) | Pertuzumab +/- Trastuzumab (Cohort 3) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 62/66 (93.9%) | 28/29 (96.6%) | ||
| Cardiac disorders | ||||
| Left ventricular dysfunction | 1/66 (1.5%) | 2/29 (6.9%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 42/66 (63.6%) | 16/29 (55.2%) | ||
| Nausea | 19/66 (28.8%) | 12/29 (41.4%) | ||
| Vomiting | 9/66 (13.6%) | 10/29 (34.5%) | ||
| Constipation | 9/66 (13.6%) | 3/29 (10.3%) | ||
| Dyspepsia | 8/66 (12.1%) | 2/29 (6.9%) | ||
| Abdominal pain upper | 5/66 (7.6%) | 4/29 (13.8%) | ||
| Abdominal distension | 3/66 (4.5%) | 3/29 (10.3%) | ||
| Abdominal pain | 4/66 (6.1%) | 2/29 (6.9%) | ||
| Stomatitis | 6/66 (9.1%) | 0/29 (0%) | ||
| Haemorroids | 4/66 (6.1%) | 0/29 (0%) | ||
| Toothache | 0/66 (0%) | 2/29 (6.9%) | ||
| General disorders | ||||
| Fatigue | 24/66 (36.4%) | 8/29 (27.6%) | ||
| Asthenia | 9/66 (13.6%) | 6/29 (20.7%) | ||
| Pyrexia | 6/66 (9.1%) | 2/29 (6.9%) | ||
| Chest pain | 5/66 (7.6%) | 2/29 (6.9%) | ||
| Chills | 4/66 (6.1%) | 3/29 (10.3%) | ||
| Mucosal inflammation | 6/66 (9.1%) | 1/29 (3.4%) | ||
| Influenza like illness | 3/66 (4.5%) | 3/29 (10.3%) | ||
| Oedema peripheral | 5/66 (7.6%) | 0/29 (0%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 8/66 (12.1%) | 1/29 (3.4%) | ||
| Upper respiratory tract infection | 3/66 (4.5%) | 3/29 (10.3%) | ||
| Localised infection | 5/66 (7.6%) | 0/29 (0%) | ||
| Rhinitis | 4/66 (6.1%) | 1/29 (3.4%) | ||
| Urinary tract infection | 4/66 (6.1%) | 1/29 (3.4%) | ||
| Investigations | ||||
| Weight decreased | 0/66 (0%) | 4/29 (13.8%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 11/66 (16.7%) | 6/29 (20.7%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 12/66 (18.2%) | 4/29 (13.8%) | ||
| Myalgia | 12/66 (18.2%) | 0/29 (0%) | ||
| Back pain | 4/66 (6.1%) | 7/29 (24.1%) | ||
| Muscle spasms | 10/66 (15.2%) | 1/29 (3.4%) | ||
| Pain in extremity | 6/66 (9.1%) | 3/29 (10.3%) | ||
| Musculoskeletal chest pain | 5/66 (7.6%) | 3/29 (10.3%) | ||
| Nervous system disorders | ||||
| Headache | 15/66 (22.7%) | 4/29 (13.8%) | ||
| Dizziness | 9/66 (13.6%) | 3/29 (10.3%) | ||
| Paraesthesia | 8/66 (12.1%) | 0/29 (0%) | ||
| Hypoaesthesia | 4/66 (6.1%) | 0/29 (0%) | ||
| Psychiatric disorders | ||||
| Insomnia | 4/66 (6.1%) | 1/29 (3.4%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 12/66 (18.2%) | 4/29 (13.8%) | ||
| Dyspnoea | 6/66 (9.1%) | 3/29 (10.3%) | ||
| Oropharyngeal pain | 3/66 (4.5%) | 3/29 (10.3%) | ||
| Rhinorrhoea | 4/66 (6.1%) | 0/29 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 18/66 (27.3%) | 5/29 (17.2%) | ||
| Pruritus | 9/66 (13.6%) | 4/29 (13.8%) | ||
| Nail disorder | 8/66 (12.1%) | 2/29 (6.9%) | ||
| Dry skin | 5/66 (7.6%) | 1/29 (3.4%) | ||
| Onychoclasis | 5/66 (7.6%) | 0/29 (0%) | ||
| Rash pruritic | 4/66 (6.1%) | 0/29 (0%) | ||
| Erythema | 1/66 (1.5%) | 2/29 (6.9%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
- BO17929
- 2005-003493-19