Trial Outcomes & Findings for A Study of Pertuzumab in Participants With Metastatic Breast Cancer (NCT NCT02491892)

Last Updated: 2015-08-25

Results Overview

Objective tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR was defined as the disappearance of all target lesions, and confirmed PR was defined as at least at 30 percent (%) decrease in the sum of the longest diameters of target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. The percentage of participants achieving a best overall response of CR or PR was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

79 participants

Primary outcome timeframe

Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response)

Results posted on

2015-08-25

Participant Flow

Participant milestones

Participant milestones
Measure	Pertuzumab 420 mg Participants received a loading dose of 840 milligrams (mg) via intravenous (IV) infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Overall Study STARTED	41	38
Overall Study Treated	41	37
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	41	38

Reasons for withdrawal

Reasons for withdrawal
Measure	Pertuzumab 420 mg Participants received a loading dose of 840 milligrams (mg) via intravenous (IV) infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Overall Study Adverse Event	1	1
Overall Study Death	1	1
Overall Study Lack of Efficacy	37	36
Overall Study Refused Treatment	1	0
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

A Study of Pertuzumab in Participants With Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pertuzumab 420 mg n=41 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.	Total n=78 Participants Total of all reporting groups
Age, Continuous	55.3 years STANDARD_DEVIATION 10.04 • n=5 Participants	53.5 years STANDARD_DEVIATION 8.72 • n=7 Participants	54.4 years STANDARD_DEVIATION 9.42 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	37 Participants n=7 Participants	78 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: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response)

Population: ITT Population.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=41 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Percentage of Participants Achieving a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR)	4.9 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response)

Population: ITT Population.

Objective tumor response was assessed using RECIST. Confirmed CR was defined as the disappearance of all target lesions, and confirmed PR was defined as at least at 30% decrease in the sum of the longest diameters of target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. Time to response was defined as the time from treatment start to first documented response (ie, CR or PR). Participants with stable disease (SD) were censored from the last tumor assessment, and those with progressive disease (PD) or death were assigned an artificial censoring time of 1000 days. Time to response was estimated using Kaplan-Meier and expressed in weeks.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=41 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Time to Response Among Participants Achieving a Best Overall Response of Confirmed CR or PR	12.1 weeks Interval 6.1 to 18.0	NA weeks Value could not be determined because no participants achieved CR or PR.

SECONDARY outcome

Timeframe: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response)

Population: ITT Population.

Objective tumor response was assessed using RECIST. Confirmed CR was defined as the disappearance of all target lesions, and confirmed PR was defined as at least at 30% decrease in the sum of the longest diameters of target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. Duration of response was defined as the time from first documented response (ie, CR or PR) to PD or death. Participants who did not experience PD or death were censored from the last tumor assessment. Duration of response was estimated using Kaplan-Meier and expressed in weeks.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=41 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Duration of Response Among Participants Achieving a Best Overall Response of Confirmed CR or PR	24.6 weeks Interval 18.1 to 31.0	NA weeks Value could not be determined because no participants achieved CR or PR.

SECONDARY outcome

Timeframe: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response)

Population: ITT Population.

Objective tumor response was assessed using RECIST. Confirmed CR was defined as the disappearance of all target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. The percentage of participants achieving a best overall response of CR was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=41 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Percentage of Participants Achieving a Best Overall Response of Confirmed CR	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response)

Population: ITT Population.

Objective tumor response was assessed using RECIST. Confirmed CR was defined as the disappearance of all target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. Duration of response was defined as the time from first documented response (ie, CR) to PD or death. Participants who did not experience PD or death were to be censored from the last tumor assessment. Duration of response was to be estimated using Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=41 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Duration of Response Among Participants Achieving a Best Overall Response of Confirmed CR	NA weeks Value could not be determined because no participants achieved CR.	NA weeks Value could not be determined because no participants achieved CR.

SECONDARY outcome

Timeframe: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response)

Population: ITT Population.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=41 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Number of Participants Who Experienced PD or Death	38 participants	36 participants

SECONDARY outcome

Timeframe: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response)

Population: ITT Population.

Objective tumor response was assessed using RECIST. PD was defined as the appearance of new lesion(s) or at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum obtained at Screening or during treatment. Participants who withdrew from the study early for insufficient therapeutic response without tumor assessment for PD were also included within the definition of PD. Time to progression was defined as the time from treatment start to PD or death. Participants who did not experience PD or death were censored from the last tumor assessment. Time to progression was estimated using Kaplan-Meier and expressed in weeks.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=41 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Time to Progression	6.1 weeks Interval 2.0 to 37.0	6.1 weeks Interval 2.7 to 36.3

SECONDARY outcome

Timeframe: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response)

Population: ITT Population.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=41 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Number of Participants Who Experienced PD or Withdrew From the Study Early	41 participants	37 participants

SECONDARY outcome

Timeframe: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response)

Population: ITT Population.

Objective tumor response was assessed using RECIST. PD was defined as the appearance of new lesion(s) or at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum obtained at Screening or during treatment. Time to treatment failure was defined as the time from treatment start to PD or early withdrawal from the study for death, toxicity, refusal/noncompliance, insufficient therapeutic response, or failure to return. Participants who did not experience PD or who did not withdraw from the study early were censored from the last tumor assessment. Time to treatment failure was estimated using Kaplan-Meier and expressed in weeks.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=41 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Time to Treatment Failure	6.3 weeks Interval 2.0 to 80.1	6.0 weeks Interval 2.7 to 36.3

SECONDARY outcome

Timeframe: Up to approximately 2 years (from start of treatment until death)

Population: Safety Population: All randomized participants who received at least one dose of pertuzumab and had at least one post-baseline safety assessment.

The percentage of participants who died was calculated as \[number of participants with event divided by the number analyzed\] multiplied by 100.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=41 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Percentage of Participants Who Died	46 percentage of participants	32 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 2 years (from start of treatment until death)

Population: Median survival was not reached because the study program was terminated early. Analysis of the incomplete data set was not performed because it could potentially produce skewed or statistically irrelevant data.

Overall survival was defined as the time from treatment start to death. Participants who did not die during follow-up were to be censored from the last known alive date. Overall survival was to be estimated using Kaplan-Meier.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response)

Population: ITT Population.

Objective tumor response was assessed using RECIST. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for PD. The percentage of participants achieving a best overall response of SD was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=41 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Percentage of Participants Achieving a Best Overall Response of SD	43.9 percentage of participants	37.8 percentage of participants

SECONDARY outcome

Timeframe: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2

Population: ITT Population. Participants with missing PK data were excluded from the analysis.

Serum samples were obtained for pharmacokinetic (PK) assessment using a receptor-binding, enzyme-linked immunosorbent assay (ELISA). Pertuzumab concentrations at each collection point were used to determine the apparent t1/2 by non-compartmental analysis, defined as the time elapsed for pertuzumab concentrations to decrease by 50%. The derived value was averaged among all participants and expressed in days.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=38 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=36 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Apparent Half-Life (t1/2) of Pertuzumab	12.2 days Standard Deviation 3.9	11.4 days Standard Deviation 4.1

SECONDARY outcome

Timeframe: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2

Population: ITT Population. Participants with missing PK data were excluded from the analysis.

Serum samples were obtained for PK assessment using a receptor-binding ELISA. The maximum observed pertuzumab concentration across all collection points was documented. Cmax was averaged among all participants and expressed in micrograms per milliliter (mcg/mL).

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=40 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Maximum Plasma Concentration (Cmax) of Pertuzumab	289 mcg/mL Standard Deviation 107	409 mcg/mL Standard Deviation 159

SECONDARY outcome

Timeframe: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2

Population: ITT Population. Participants with missing PK data were excluded from the analysis.

Serum samples were obtained for PK assessment using a receptor-binding ELISA. The time of maximum observed pertuzumab concentration across all collection points was documented. Tmax was averaged among all participants and expressed in days.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=40 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Time to Maximum Plasma Concentration (Tmax) of Pertuzumab	0.073 days Interval 0.052 to 7.0	0.073 days Interval 0.059 to 0.122

SECONDARY outcome

Timeframe: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2

Population: ITT Population. Participants with missing PK data were excluded from the analysis, and the number of participants analyzed (n) is presented here.

Serum samples were obtained for PK assessment using a receptor-binding ELISA. Pertuzumab concentrations at each collection point were used to determine AUC to the last measurable observation (AUClast) and AUC extrapolated to infinity (AUCinf) by non-compartmental analysis. The derived values were averaged among all participants and expressed in days by micrograms per milliliter (days\*mcg/mL).

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=40 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Area Under the Concentration-Time Curve (AUC) of Pertuzumab AUClast (n=40,37)	2517 days*mcg/mL Standard Deviation 896	3465 days*mcg/mL Standard Deviation 1051
Area Under the Concentration-Time Curve (AUC) of Pertuzumab AUCinf (n=38,36)	3598 days*mcg/mL Standard Deviation 1402	4750 days*mcg/mL Standard Deviation 1527

SECONDARY outcome

Timeframe: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2

Population: ITT Population. Participants with missing PK data were excluded from the analysis.

Serum samples were obtained for PK assessment using a receptor-binding ELISA. Pertuzumab concentrations at each collection point were used to determine CL by non-compartmental analysis, defined as the rate at which pertuzumab was removed from the body. The derived value was averaged among all participants and expressed in milliliters per day (mL/day).

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=38 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=36 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Systemic Clearance (CL) of Pertuzumab	270 mL/day Standard Deviation 113	247 mL/day Standard Deviation 90

SECONDARY outcome

Timeframe: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2

Population: ITT Population. Participants with missing PK data were excluded from the analysis.

Serum samples were obtained for PK assessment using a receptor-binding ELISA. Pertuzumab concentrations at each collection point were used to determine the Vss by non-compartmental analysis, defined as the theoretical volume at which the total amount of pertuzumab would be uniformly distributed to produce the desired concentration. The derived value was averaged among all participants and expressed in milliliters (mL).

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=38 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=36 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Volume of Distribution at Steady State (Vss) of Pertuzumab	4122 mL Standard Deviation 1666	3527 mL Standard Deviation 1369

SECONDARY outcome

Timeframe: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2

Population: ITT Population. Participants with missing PK data were excluded from the analysis.

Serum samples were obtained for PK assessment using a receptor-binding ELISA. Pertuzumab concentrations at each collection point were used to determine the MRT by non-compartmental analysis. The derived value was averaged among all participants and expressed in days.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=38 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=36 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Mean Residence Time (MRT) of Pertuzumab	16 days Standard Deviation 5	15 days Standard Deviation 6

SECONDARY outcome

Timeframe: Up to approximately 1 year (at Baseline; at the end of Cycles 2, 4, 8, 12, and 16; and up to 7 weeks following the last infusion)

Population: Safety Population.

Echocardiography was performed to determine LVEF, defined as the volume of blood pumped from the left ventricle as a percentage of end-diastolic volume. Theoretically, LVEF may range from 0 to 100%. The number of participants experiencing a drop in LVEF greater than or equal to (≥) 10 or 15 percentage points to a final LVEF of less than (\<) 50% is reported here.

Outcome measures

Outcome measures
Measure	Pertuzumab 420 mg n=41 Participants Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 Participants Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Number of Participants Experiencing a Drop in Left Ventricular Ejection Fraction (LVEF) to a Value of Less Than 50% Drop ≥10 percentage points	3 participants	5 participants
Number of Participants Experiencing a Drop in Left Ventricular Ejection Fraction (LVEF) to a Value of Less Than 50% Drop ≥15 percentage points	3 participants	3 participants

Adverse Events

Pertuzumab 420 mg

Serious events: 10 serious events

Other events: 36 other events

Deaths: 0 deaths

Pertuzumab 1050 mg

Serious events: 8 serious events

Other events: 37 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 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Pertuzumab 420 mg n=41 participants at risk Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 participants at risk Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Gastrointestinal disorders Ascites	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	2.7% 1/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Gastrointestinal disorders Diarrhoea	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	2.7% 1/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Gastrointestinal disorders Dysphagia	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	2.7% 1/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	2.7% 1/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Infections and infestations Lung infection	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	0.00% 0/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Infections and infestations Pneumonia	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	0.00% 0/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Infections and infestations Sepsis	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	0.00% 0/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	2.7% 1/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	2.7% 1/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Cardiac disorders Cardiac failure	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	0.00% 0/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Cardiac disorders Pericardial effusion	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	0.00% 0/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Investigations Ejection fraction decreased	4.9% 2/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	0.00% 0/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	2.7% 1/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	2.7% 1/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Musculoskeletal and connective tissue disorders Neck pain	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	0.00% 0/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Nervous system disorders Headache	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	0.00% 0/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)

Measure	Pertuzumab 420 mg n=41 participants at risk Participants received a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.	Pertuzumab 1050 mg n=37 participants at risk Participants did not receive a loading dose, but received pertuzumab 1050 mg via IV infusion every 3 weeks until unacceptable toxicity or disease progression.
Gastrointestinal disorders Diarrhoea	58.5% 24/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	59.5% 22/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Gastrointestinal disorders Nausea	29.3% 12/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	35.1% 13/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
General disorders Asthenia	24.4% 10/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	24.3% 9/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Gastrointestinal disorders Vomiting	24.4% 10/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	21.6% 8/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Gastrointestinal disorders Abdominal pain upper	14.6% 6/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	16.2% 6/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Metabolism and nutrition disorders Anorexia	9.8% 4/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	21.6% 8/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Nervous system disorders Headache	17.1% 7/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	13.5% 5/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.2% 5/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	13.5% 5/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
General disorders Fatigue	12.2% 5/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	13.5% 5/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Skin and subcutaneous tissue disorders Rash	14.6% 6/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	10.8% 4/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Gastrointestinal disorders Stomatitis	9.8% 4/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	10.8% 4/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Blood and lymphatic system disorders Anaemia	7.3% 3/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	10.8% 4/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Musculoskeletal and connective tissue disorders Arthralgia	7.3% 3/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	10.8% 4/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Musculoskeletal and connective tissue disorders Back pain	9.8% 4/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	8.1% 3/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
General disorders Chest pain	4.9% 2/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	13.5% 5/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Gastrointestinal disorders Dyspepsia	7.3% 3/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	8.1% 3/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Investigations Ejection fraction decreased	7.3% 3/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	8.1% 3/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
General disorders Mucosal inflammation	9.8% 4/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Gastrointestinal disorders Abdominal pain	9.8% 4/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	2.7% 1/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Respiratory, thoracic and mediastinal disorders Cough	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	10.8% 4/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Skin and subcutaneous tissue disorders Dry skin	9.8% 4/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	2.7% 1/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Nervous system disorders Paraesthesia	7.3% 3/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Nervous system disorders Dizziness	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	8.1% 3/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Respiratory, thoracic and mediastinal disorders Epistaxis	4.9% 2/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	4.9% 2/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.9% 2/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Skin and subcutaneous tissue disorders Pruritus	4.9% 2/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Infections and infestations Urinary tract infection	4.9% 2/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Nervous system disorders Dysgeusia	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	8.1% 3/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Renal and urinary disorders Dysuria	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Infections and infestations Herpes simplex	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Psychiatric disorders Insomnia	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	8.1% 3/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Gastrointestinal disorders Oesophagitis	2.4% 1/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
General disorders Pyrexia	7.3% 3/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	0.00% 0/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Gastrointestinal disorders Dysphagia	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Infections and infestations Ear infection	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Skin and subcutaneous tissue disorders Erythema	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Gastrointestinal disorders Irritable bowel syndrome	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)
Infections and infestations Nasopharyngitis	0.00% 0/41 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)	5.4% 2/37 • Up to approximately 1 year (from start of treatment until up to 7 weeks following the last infusion)