Trial Outcomes & Findings for A Study to Evaluate the Effect of the Combination of Pertuzumab With Carboplatin-Based Standard Chemotherapy in Patients With Recurrent Ovarian Cancer (NCT NCT02004093)

NCT ID: NCT02004093

Last Updated: 2014-12-04

Results Overview

Disease progression was assessed according to RECIST (Response Evaluation Criteria In Solid Tumors), for participants with measurable disease, or by changes in CA 125 (Cancer Antigen 125) according to GCIG (Gynecologic Cancer Inter Group) for all participants. Participants who did not progress or died while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

149 participants

Primary outcome timeframe

Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks

Results posted on

2014-12-04

Participant Flow

Participant milestones

Participant milestones
Measure	Chemotherapy + Pertuzumab Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 milligrams (mg) intravenously (IV) on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/square meters (m\^2) IV on Day 1 and carboplatin target area under the curve (AUC) 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Overall Study STARTED	75	74
Overall Study COMPLETED	1	1
Overall Study NOT COMPLETED	74	73

Reasons for withdrawal

Reasons for withdrawal
Measure	Chemotherapy + Pertuzumab Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 milligrams (mg) intravenously (IV) on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/square meters (m\^2) IV on Day 1 and carboplatin target area under the curve (AUC) 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Overall Study Death	2	1
Overall Study Lack of Efficacy	66	62
Overall Study Protocol Violation	0	1
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	3	7
Overall Study Other	3	1

Baseline Characteristics

A Study to Evaluate the Effect of the Combination of Pertuzumab With Carboplatin-Based Standard Chemotherapy in Patients With Recurrent Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chemotherapy + Pertuzumab n=74 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER: 1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=75 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Total n=149 Participants Total of all reporting groups
Age, Continuous	58.1 years STANDARD_DEVIATION 10.16 • n=5 Participants	55.3 years STANDARD_DEVIATION 11.41 • n=7 Participants	56.7 years STANDARD_DEVIATION 10.86 • n=5 Participants
Sex: Female, Male Female	74 Participants n=5 Participants	75 Participants n=7 Participants	149 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks

Population: All treated participants who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis.

Outcome measures

Outcome measures
Measure	Chemotherapy + Pertuzumab n=74 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=75 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Percentage of Participants With Disease Progression or Death	87.8 percentage of participants	80.0 percentage of participants

PRIMARY outcome

Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks

Population: All treated patients who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis.

Progression-free survival was defined as the time from first administration of study drug (Study Day 1) to documented disease progression or death, whichever occurred earlier. Disease progression was assessed according to RECIST, for participants with measurable disease, or by changes in CA 125 according to GCIG for all participants. Participants who did not progress or died while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment.

Outcome measures

Outcome measures
Measure	Chemotherapy + Pertuzumab n=74 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=75 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Progression-Free Survival	34.1 weeks Interval 31.0 to 38.0	40.0 weeks Interval 33.0 to 43.0

PRIMARY outcome

Timeframe: 1 year

Population: All treated patients who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis. 17 and 12 participants in the chemotherapy + pertuzumab and chemotherapy treatment groups, respectively, remained at risk.

The probability of being event free (no disease progression or death events) at 1 year in participants remaining at risk.

Outcome measures

Outcome measures
Measure	Chemotherapy + Pertuzumab n=74 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=75 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Kaplan-Meier Probability of No Disease or Progression at 1 Year	24 percent	21 percent

SECONDARY outcome

Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks

Population: All treated patients who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis.

Response by tumor measurement occurred if there was documented and confirmed complete response (CR) or partial response (PR). For all participants, response was assessed by both the RECIST and by CA 125 levels, according to whether the participant had measurable or non-measurable disease at baseline. Response according to CA 125 levels was defined as at least a 50% reduction from baseline. The decrease had to be confirmed and maintained for at least 28 days. The confirmatory sample must have been less than or equal to the previous sample (within an assay variability of 10%). For overall response, the response categories were "response", "stable disease" and "progressive disease". Stable disease included 1) stable disease as defined by RECIST for solid tumors and 2) CA 125 levels that had not met the definition of "response" or "progressive disease".

Outcome measures

Outcome measures
Measure	Chemotherapy + Pertuzumab n=74 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=75 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Percentage of Participants With a Best Overall Confirmed Response Based on Combined CA 125 and RECIST Measurements	74.3 percentage of participants	68.0 percentage of participants

SECONDARY outcome

Timeframe: Day 15 of Cycles 2, 4, 6, and Day 15 of all Cycles from Cycle 7 to 17 until disease progression up to 104 weeks

Population: Only participants with a response were included in the analysis; 8 participants and 13 participants were censored in the chemotherapy + pertuzumab and chemotherapy only treatment groups, respectively.

For participants who achieved a response, the duration of response was defined as the interval between initial documentation of response to the first documentation of disease progression or death. Participants who responded and did not progress or die while on study or while being followed were censored at the last valid tumor or CA 125 measurement.

Outcome measures

Outcome measures
Measure	Chemotherapy + Pertuzumab n=47 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=38 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Duration of Response	28.7 weeks Interval 22.0 to 48.0	37.0 weeks Interval 25.0 to 43.0

SECONDARY outcome

Timeframe: 1 year

Population: All treated patients who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis. 7 and 5 participants in the chemotherapy + pertuzumab and chemotherapy treatment groups, respectively, remained at risk.

Outcome measures

Outcome measures
Measure	Chemotherapy + Pertuzumab n=55 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=51 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Kaplan-Meier Probability of Maintaining a Response to at Least 1 Year	18 percent	18 percent

SECONDARY outcome

Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression

Population: All treated participants were included in analysis

Disease progression was assessed according to RECIST, for participants with measurable disease, or by changes in CA 125 according to GCIG for all participants. Participants who did not progress while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment.

Outcome measures

Outcome measures
Measure	Chemotherapy + Pertuzumab n=74 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=75 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Percentage of Participants With Disease Progression	83.8 percentage of participants	76.0 percentage of participants

SECONDARY outcome

Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression

Population: All treated patients with an event (disease progression) were included in analysis

The time to progressive disease is the interval of time from date of first dose of study medication to date of first documentation of progressive disease by either RECIST or CA 125 criteria. Participants who never progressed while being followed were censored at the last valid tumor measurement or CA 125 measurement.

Outcome measures

Outcome measures
Measure	Chemotherapy + Pertuzumab n=62 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=57 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Time to Progressive Disease	34.3 weeks Interval 27.0 to 48.0	37.3 weeks Interval 29.0 to 47.0

SECONDARY outcome

Timeframe: 1 year

Population: All treated patients who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis. 16 and 10 participants in the chemotherapy + pertuzumab and chemotherapy treatment groups, respectively, remained at risk.

Outcome measures

Outcome measures
Measure	Chemotherapy + Pertuzumab n=62 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=57 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Kaplan-Meier Probability of Being Progression Free at 1 Year	24 percent	19 percent

SECONDARY outcome

Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment

Population: Only participants with a response were included in the analysis.

Time to response was the date of first dose of study medication to the date of the first documentation of response, according to CA 125 criteria for all participants or response according to RECIST criteria for participants with measurable disease. If response was evaluable by both criteria, then the date of response was for the earlier of the two events.

Outcome measures

Outcome measures
Measure	Chemotherapy + Pertuzumab n=55 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=51 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Time To Response	6.0 weeks Interval 5.0 to 17.0	6.3 weeks Interval 5.0 to 15.0

SECONDARY outcome

Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment

Population: All treated participants were included in analysis

Outcome measures

Outcome measures
Measure	Chemotherapy + Pertuzumab n=74 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=75 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Percentage of Participants Who Died	45.9 percentage of participants	41.3 percentage of participants

SECONDARY outcome

Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment

Population: All treated participants were included in analysis

Survival was the interval of time from date of first dose of study medication to date of death at any time. Participants who had not died were censored at the date of last contact when they were known to be alive.

Outcome measures

Outcome measures
Measure	Chemotherapy + Pertuzumab n=74 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=75 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Overall Survival	28.2 months Interval 1.0 to 52.0	NA months Interval 1.0 to 34.0 Given the duration of follow-up at time of data analysis the median had not been reached and could not be calculated (at least 50% of patients had not died).

SECONDARY outcome

Timeframe: 1 year

Population: All treated patients who received Randomized Treatment (All Treated Population, for Efficacy Analyses) were included in analysis.

Outcome measures

Outcome measures
Measure	Chemotherapy + Pertuzumab n=64 Participants Participants received pertuzumab for a total of seventeen 3-week cycles and chemotherapy for a total of six 3-week cycles. Pertuzumab: Participants received pertuzumab 840 mg IV on Day 1 of cycle 1 and 420 mg IV on Day 1 of cycles 2 to 17; Chemotherapy consisted of EITHER:1) paclitaxel 175 mg/m\^2 IV on Day 1 and carboplatin target AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.	Chemotherapy n=61 Participants Participants received chemotherapy with EITHER: 1) paclitaxel 175 mg/m\^2 on Day 1 and carboplatin AUC 5, IV, on Day 1 followed by 2 weeks off OR 2) gemcitabine 1000 mg/m\^2, IV, on Days 1 and 8 (with carboplatin target AUC of 4, IV on Day 1 only) followed by 1 week off.
Kaplan-Meier Probability of Being Alive at 1 Year	88 percent	85 percent

Adverse Events

Chemotherapy + Pertuzumab

Serious events: 20 serious events

Other events: 72 other events

Deaths: 0 deaths

Chemotherapy

Serious events: 12 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann- LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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 after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Chemotherapy + Pertuzumab n=75 participants at risk Participants received loading dose of 840mg IV Pertuzumab, followed by 420 mg IV every 3 weeks (for a total of 17 cycles), along with chemotherapy with either Paclitaxel or Gemcitabine. Paclitaxel dosage was 175 mg/m2 IV every 3 weeks for 6 cycles, followed by Carboplatin AUC of 5; Gemcitabine dosage was 1000 mg/m2 IV on day 1 and 8 of each cycle for 6 cycles followed by Carboplatin AUC of 4, IV every 3 weeks for 6 cycles.	Chemotherapy n=74 participants at risk Participants received chemotherapy with either Paclitaxel or Gemcitabine. Paclitaxel dosage was 175 mg/m2 IV every 3 weeks for 6 cycles followed by Carboplatin AUC of 5; Gemcitabine dosage was 1000 mg/ m2 IV on day 1 and 8 of each cycle for 6 cycles followed by Carboplatin AUC of 4, IV every 3 weeks for 6 cycles.
Gastrointestinal disorders Ileus paralytic	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Gastrointestinal disorders Large intesting perforation	0.00% 0/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	1.4% 1/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Infections and infestations Appendicitis	0.00% 0/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	1.4% 1/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Infections and infestations Lower respiratory tract infection	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Infections and infestations Pneumonia	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Infections and infestations Sinusitis	0.00% 0/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	1.4% 1/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	4.1% 3/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Blood and lymphatic system disorders Anaemia	0.00% 0/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	1.4% 1/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
General disorders Pyrexia	2.7% 2/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
General disorders Local swelling	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Infections and infestations Cystitis	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Gastrointestinal disorders Abdominal pain	2.7% 2/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	1.4% 1/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Gastrointestinal disorders Ascites	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	1.4% 1/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Gastrointestinal disorders Diarrhoea	2.7% 2/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Gastrointestinal disorders Intestinal obstruction	2.7% 2/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Gastrointestinal disorders Vomiting	2.7% 2/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Gastrointestinal disorders Constipation	0.00% 0/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	1.4% 1/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
General disorders Obstruction	0.00% 0/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	1.4% 1/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Immune system disorders Drug hypersensitivity	5.3% 4/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	1.4% 1/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Respiratory, thoracic and mediastinal disorders Diaphragmatic hernia	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Cardiac disorders Cardiac failure congestive	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Cardiac disorders Left ventricular dysfunction	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Nervous system disorders Neuropathy peripheral	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Nervous system disorders Syncope	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Hepatobiliary disorders Hepatic lesion	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Investigations Blood glucose increased	1.3% 1/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	0.00% 0/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.
Metabolism and nutrition disorders Dehydration	0.00% 0/75 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.	1.4% 1/74 • Adverse events were collected from the date of randomization until 28 days after the last dose of the pertuzumab and/ or standard chemotherapy and continuously until end of study.