Safety Study of Pertuzumab (in Combination With Trastuzumab and Docetaxel) in Indian Participants With Breast Cancer

A Phase IV, Multicenter, Open-Label, Single-Arm Study of Pertuzumab (in Combination With Trastuzumab and Docetaxel) in First Line Treatment of Indian Patients With HER2-Positive Advanced (Metastatic or Locally Recurrent) Breast Cancer

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02445586

Enrollment

Registered

2015-05-15

Start date

2015-08-17

Completion date

2018-09-26

Last updated

2019-10-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

Brief summary

This is a Phase 4, single-arm, open-label, multicenter study to assess the safety and efficacy of pertuzumab in combination with trastuzumab and docetaxel for the treatment of participants with human epidermal growth factor receptor 2 (HER2)-positive advanced (locally recurrent, unresectable, or metastatic) breast cancer.

Interventions

DRUGTrastuzumab

Participants will receive trastuzumab at an initial dose of 8 milligrams per kilogram (mg/kg) as a 90-minute intravenous infusion on Cycle 1 Day 1 (cycle length = 21 days), followed by every 3 weeks at a dose of 6 mg/kg as a 30 to 90-minute intravenous infusion until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

DRUGDocetaxel

Participants will receive docetaxel in line with locally approved Prescribing Information. After Cycle 6 (cycle length = 21 days), continuation of docetaxel treatment will be at the discretion of the investigator. Docetaxel will be administered after pertuzumab and trastuzumab.

DRUGPertuzumab

Participants will receive pertuzumab at an initial dose of 840 milligrams (mg) as a 60-minute intravenous infusion on Cycle 1 Day 1 (cycle length = 21 days), followed by every 3 weeks at a dose of 420 mg as a 30 to 60-minute intravenous infusion until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly-effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the participant and/or partner * Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative resection; participants with measurable and/or non-measurable disease are eligible * Known and documented HER2-positive * Known and documented LVEF of at least 50 percent (%) * Adequate organ function * A negative serum beta-human chorionic gonadotropin (beta-HCG) test for women of childbearing potential (premenopausal, or less than \[\<\] 12 months of amenorrhea post-menopause, and women who have not undergone surgical sterilization \[absence of ovaries and/or uterus\]) within 7 days prior to the first dose of study treatment with the result available prior to first dosing

Exclusion criteria

* Previous systemic non-hormonal anti-cancer therapy for the metastatic or locally recurrent disease * Pregnant or lactating women * Current clinical or radiographic evidence of central nervous system (CNS) metastases * Disease progression while receiving or within 12 months of completion of trastuzumab and/or lapatinib treatment in the adjuvant or neo-adjuvant setting * History of LVEF decline to below 50% during or after prior trastuzumab adjuvant or neo-adjuvant therapy

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Adverse Events Leading to Treatment Discontinuation	From Baseline until end of study (up to approximately 3 years)	The number of participants with any adverse event (serious or non-serious) that led to treatment discontinuation during the study was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one adverse event that led to treatment discontinuation may have been reported per participant.
Overall Number of Participants With Non-Serious Adverse Events by Event Outcome	From Baseline until end of study (up to approximately 3 years)	The number of participants with non-serious adverse events was counted by the event outcome in the four following categories: resolved with no sequelae, resolved with sequelae, unresolved, or death. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events with the same outcome were only counted once per category.
Overall Number of Participants With Non-Serious Adverse Events by Treatment Emergence (TEAE Versus Non-TEAE)	From Baseline until end of study (up to approximately 3 years)	The number of participants with non-serious adverse events was counted according to whether the event was considered a treatment emergent adverse event (TEAE), which is defined as an adverse event that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state. Participants with multiple occurrences of non-serious adverse events were only counted once per category.
Number of Participants With Hematological Abnormalities Reported as Non-Serious Adverse Events	From Baseline until end of study (up to approximately 3 years)	The number of participants with hematological laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Number of Participants With Serum Chemistry Abnormalities Reported as Non-Serious Adverse Events	From Baseline until end of study (up to approximately 3 years)	The number of participants with serum chemistry laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Number of Participants With Coagulation Abnormalities Reported as Non-Serious Adverse Events	From Baseline until end of study (up to approximately 3 years)	The number of participants with coagulation laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Number of Participants With Congestive Heart Failure	From Baseline until end of study (up to approximately 3 years)	—
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Baseline, every 3 cycles (1 cycle is 21 days) until treatment discontinuation, at Safety Follow-Up (28 days after last dose of study drug) and every 3 months thereafter until end of study (up to approximately 3 years)	Left ventricular ejection fraction (LVEF) assessments were performed within 42 days of enrollment and every three treatment cycles by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan; ECHO was the preferred method. In order to be eligible for this study, an LVEF of ≥50% was required at screening. The same method of LVEF assessment for each participant must have been used throughout the study, and to the extent possible, have been obtained at the same institution.
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Baseline, every 3 cycles (1 cycle is 21 days) until treatment discontinuation, at Safety Follow-Up (28 days after last dose of study drug) and every 3 months thereafter until end of study (up to approximately 3 years)	Left ventricular ejection fraction (LVEF) assessments were performed within 42 days of enrollment and every three treatment cycles by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan; ECHO was the preferred method. In order to be eligible for this study, an LVEF greater than or equal to (≥)50% was required at screening. The same method of LVEF assessment for each participant must have been used throughout the study, and to the extent possible, have been obtained at the same institution. The following are definitions for the three categories of LVEF findings: 'Normal' was defined as LVEF ≥45%; 'Abnormal but not clinically significant' was defined as LVEF \<45% but not clinically significant in the investigator's judgment; 'Abnormal and clinically significant' was defined as LVEF \<45% and clinically significant in the investigator's judgment.
Overall Number of Participants by the Number of Serious Adverse Events Reported Per Participant	From Baseline until end of study (up to approximately 3 years)	The number of participants with serious adverse events was counted in the four following categories for number of events reported per participant: greater than or equal to (≥) 1, 1, greater than (\>) 1, or 0 serious adverse events. Participants with multiple occurrences of events (the ≥1 and \>1 serious adverse event categories) were only counted once per category.
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)	From Baseline until end of study (up to approximately 3 years)	The number of participants with serious adverse events was counted by the initial and most extreme levels of severity of the adverse event, assessed as Grades 1-5 according to NCI CTCAE v4.03. Any adverse event not specifically listed in NCI CTCAE v4.03 was assessed according to the following grades of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening or urgent intervention indicated; and Grade 5 is death related to adverse event. The terms severe and serious are not synonymous. Severity refers to the intensity of an adverse event. The seriousness of an adverse event is based on whether it meets any of the criteria set out in the protocol's definition of a serious adverse event. Severity and seriousness were independently assessed for each adverse event. Participants with multiple occurrences of serious adverse events of the same severity were only counted once per severity category.
Number of Participants With Serious Adverse Events Related to Docetaxel	From Baseline until end of study (up to approximately 3 years)	The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with docetaxel, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Number of Participants With Serious Adverse Events Related to Pertuzumab	From Baseline until end of study (up to approximately 3 years)	The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with pertuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Number of Participants With Serious Adverse Events Related to Trastuzumab	From Baseline until end of study (up to approximately 3 years)	The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with trastuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug	From Baseline until end of study (up to approximately 3 years)	The number of participants with serious adverse events was counted by the type of action taken with the study drug (docetaxel, pertuzumab, and trastuzumab) in response to the adverse event in the three following categories: infusion reduced, temporarily interrupted, or permanently discontinued. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of serious adverse events that required the same action to be taken with the study drug were only counted once per category.
Overall Number of Participants With Serious Adverse Events by Event Outcome	From Baseline until end of study (up to approximately 3 years)	The number of participants with serious adverse events was counted by the event outcome in the six following categories: fatal, recovered/resolved, recovered/resolved with sequelae, recovering/resolving, not recovered/not resolved, or unknown. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of serious adverse events with the same outcome were only counted once per category.
Number of Participants With Hematological Abnormalities Reported as Serious Adverse Events	From Baseline until end of study (up to approximately 3 years)	The number of participants with hematological laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Number of Participants With Serum Chemistry Abnormalities Reported as Serious Adverse Events	From Baseline until end of study (up to approximately 3 years)	The number of participants with serum chemistry laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Number of Participants With Coagulation Abnormalities Reported as Serious Adverse Events	From Baseline until end of study (up to approximately 3 years)	The number of participants with coagulation laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Number of Participants Who Died Due to a Serious Adverse Event by Cause of Death	From Baseline until end of study (up to approximately 3 years)	The number of participants who died due to a serious adverse event was counted by the cause of death.
Overall Number of Participants by the Number of Non-Serious Adverse Events Reported Per Participant	From Baseline until end of study (up to approximately 3 years)	The number of participants with non-serious adverse events was counted in the four following categories for number of events reported per participant: greater than or equal to (≥) 1, 1, greater than (\>) 1, or 0 non-serious adverse events. Participants with multiple occurrences of events (the ≥1 and \>1 non-serious adverse event categories) were only counted once per category.
Overall Number of Participants With Non-Serious Adverse Events by Severity, According to NCI-CTCAE v4.03	From Baseline until end of study (up to approximately 3 years)	The number of participants with non-serious adverse events was counted by the severity level of the adverse event, assessed as Grades 1-5 according to NCI CTCAE v4.03. Any adverse event not specifically listed in NCI CTCAE v4.03 was assessed according to the following grades of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening or urgent intervention indicated; and Grade 5 is death related to adverse event. The terms severe and serious are not synonymous. Severity refers to the intensity of an adverse event. The seriousness of an adverse event is based on whether it meets any of the criteria set out in the protocol's definition of a serious adverse event. Severity and seriousness were independently assessed for each adverse event. Participants with multiple occurrences of non-serious adverse events of the same severity were only counted once per severity category.
Number of Participants With Non-Serious Adverse Events Related to Docetaxel	From Baseline until end of study (up to approximately 3 years)	The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with docetaxel, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab	From Baseline until end of study (up to approximately 3 years)	The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with pertuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Number of Participants With Non-Serious Adverse Events Related to Trastuzumab	From Baseline until end of study (up to approximately 3 years)	The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with trastuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Overall Number of Participants With Non-Serious Adverse Events by Chemotherapy Adjustment With Docetaxel and/or Trastuzumab	From Baseline until end of study (up to approximately 3 years)	The number of participants with non-serious adverse events was counted by the type of action taken with docetaxel and/or trastuzumab in response to the adverse event in the three following categories: no adjustment, dosage modified/interrupted, and discontinued. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events that required the same action to be taken with the study drug were only counted once per category.
Overall Number of Participants With Non-Serious Adverse Events by Action Taken With Pertuzumab	From Baseline until end of study (up to approximately 3 years)	The number of participants with non-serious adverse events was counted by the type of action taken with pertuzumab in response to the adverse event in the three following categories: no action taken, infusion slow down, infusion interrupted, and appropriate medical therapies administered. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events that required the same action to be taken with the study drug were only counted once per category.

Secondary

Measure	Time frame	Description
Number of Participants by Best Overall Response	From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)	The best overall response was defined as the best response, out of all the documented responses over the course of the entire study period, using RECIST v1.1. All measurable and non-measurable lesions were documented at screening and re-assessed at each subsequent tumor evaluation. Response was assessed by the investigator on the basis of physical examinations, computed tomography (CT) scans, and magnetic resonance imaging (MRI). The same radiographic procedure was used throughout the study, and assessments were preferably performed by the same evaluator.
Number of Participants With Disease Progression or Death or Who Were Censored for Progression-Free Survival Analysis	From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)	Progression-free survival (PFS) was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Participants who had not progressed or died or were lost to follow up at the time of the analysis were censored on the last visit at which assessment for progression was done (2 years after the last participant was enrolled). PFS was analyzed by the Kaplan-Meier method.
Median Duration of Progression-Free Survival	From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)	Progression-free survival (PFS) was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Participants who had not progressed or died, or were lost to follow up at the time of the analysis, were censored on the last visit at which assessment for progression was done (2 years after the last participant was enrolled). PFS was analyzed by the Kaplan-Meier method.
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months	Months 2, 3, 5, 6, 7, 8, 9, 11, 13, 15, 16, 17, 18, 19, 23, 24, 25, 27, 29, and 32	Progression-free survival (PFS) was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Participants who had not progressed, died or were lost to follow up at the time of the analysis were censored on the last visit at which assessment for progression was done (2 years after the last participant was enrolled). PFS was analyzed by the Kaplan-Meier method.
Number of Participants Who Died or Were Censored for Overall Survival Analysis	From Baseline up to death from any cause (up to approximately 3 years)	Overall survival was defined as the time from enrollment to the the date of death from any cause. Participants who were alive at the time of the analysis, dropped out of the study, or lost to follow-up were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication, and participants with no post-baseline information were censored at baseline. Overall survival was analyzed by the Kaplan-Meier method.
Median Duration of Overall Survival	From Baseline up to death from any cause (up to approximately 3 years)	Overall survival was defined as the time from enrollment to the the date of death from any cause. Participants who were alive at the time of the analysis, dropped out of the study, or lost to follow-up were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication, and participants with no post-baseline information were censored at baseline. Overall survival was analyzed by the Kaplan-Meier method.
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months	Months 3, 9, 13, 14, 15, 18, 19, 20, 24, 25, 27, 32, 33, and 34	Overall survival was defined as the time from enrollment to the the date of death from any cause. Participants who were alive at the time of the analysis, dropped out of the study, or lost to follow-up were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication, and participants with no post-baseline information were censored at baseline. Overall survival was analyzed by the Kaplan-Meier method.
Overall Response Rate	From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)	The overall response rate (ORR) was defined as the percentage of participants with best overall response of Complete Response (CR) or Partial Response (PR), confirmed by repeat assessment no less than 4 weeks after the response criteria were first met, using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Participants who either had not achieved CR or PR or were without a post-baseline tumor assessment were to be considered non-responders. All measurable and non-measurable lesions were documented at screening and re-assessed at each subsequent tumor evaluation. Response was assessed by the investigator on the basis of physical examinations, computed tomography (CT) scans, and magnetic resonance imaging (MRI). The same radiographic procedure was used throughout the study, and assessments were preferably performed by the same evaluator. The 95% confidence intervals were calculated using Clopper-Pearson methodology.

Countries

India

Participant flow

Participants by arm

Arm	Count
Pertuzumab in Combination With Trastuzumab and Docetaxel Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.	52
Total	52

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	14
Overall Study	Disease Progression	10
Overall Study	Medical Condition	1
Overall Study	Protocol Violation	1
Overall Study	Withdrawal by Subject	13

Baseline characteristics

Characteristic	Pertuzumab in Combination With Trastuzumab and Docetaxel
Age, Continuous	50.2 years STANDARD_DEVIATION 9.05
Any Previous Therapy for Breast Cancer No	33 Participants
Any Previous Therapy for Breast Cancer Yes	19 Participants
Breast Cancer Subtype by Histology Ductal	47 Participants
Breast Cancer Subtype by Histology Lobular	0 Participants
Breast Cancer Subtype by Histology Other	5 Participants
Diagnosis of Metastatic or Locally Recurrent Breast Cancer Locally Recurrent	0 Participants
Diagnosis of Metastatic or Locally Recurrent Breast Cancer Metastatic	52 Participants
HER2 Expression Score by IHC 0	0 Participants
HER2 Expression Score by IHC 1+	0 Participants
HER2 Expression Score by IHC 2+	4 Participants
HER2 Expression Score by IHC 3+	47 Participants
HER2 Expression Score by IHC Assessment Missing	1 Participants
HER2 Expression Score by ISH Negative (Non-Amplified)	1 Participants
HER2 Expression Score by ISH Not Assessed by ISH	31 Participants
HER2 Expression Score by ISH Positive (Amplified)	20 Participants
HER2-Positive Breast Cancer Confirmation Method Both IHC and ISH	20 Participants
HER2-Positive Breast Cancer Confirmation Method Immunohistochemistry (IHC)	31 Participants
HER2-Positive Breast Cancer Confirmation Method In Situ Hybridization (ISH)	1 Participants
Histological Grade of Breast Cancer Anaplastic	0 Participants
Histological Grade of Breast Cancer Moderately Differentiated	16 Participants
Histological Grade of Breast Cancer Poorly Differentiated	11 Participants
Histological Grade of Breast Cancer Unknown	11 Participants
Histological Grade of Breast Cancer Well Differentiated	14 Participants
Hormone Receptor Status (Positive or Negative) Estrogen Receptor Negative	31 Participants
Hormone Receptor Status (Positive or Negative) Estrogen Receptor Positive	21 Participants
Hormone Receptor Status (Positive or Negative) Progesterone Receptor Negative	34 Participants
Hormone Receptor Status (Positive or Negative) Progesterone Receptor Positive	18 Participants
Presence or Absence of Ductal Carcinoma In Situ (DCIS) DCIS Absent	29 Participants
Presence or Absence of Ductal Carcinoma In Situ (DCIS) DCIS Assessment Missing	1 Participants
Presence or Absence of Ductal Carcinoma In Situ (DCIS) DCIS Present	22 Participants
Race/Ethnicity, Customized Ethnicity: Indian Subcontinent	52 Participants
Race/Ethnicity, Customized Race: Asian	52 Participants
Sex: Female, Male Female	52 Participants
Sex: Female, Male Male	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	15 / 52
other Total, other adverse events	47 / 52
serious Total, serious adverse events	31 / 52

Outcome results

Primary

Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time

Time frame: Baseline, every 3 cycles (1 cycle is 21 days) until treatment discontinuation, at Safety Follow-Up (28 days after last dose of study drug) and every 3 months thereafter until end of study (up to approximately 3 years)

Population: Safety Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Baseline (BL) - Value at Visit	59.6 percentage points of LVEF	Standard Deviation 3.92
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 3	-0.7 percentage points of LVEF	Standard Deviation 2.95
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 6	-0.8 percentage points of LVEF	Standard Deviation 4.09
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 9	-0.2 percentage points of LVEF	Standard Deviation 4.43
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 12	0.2 percentage points of LVEF	Standard Deviation 3.99
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 15	-0.8 percentage points of LVEF	Standard Deviation 4.33
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 18	-1.3 percentage points of LVEF	Standard Deviation 4.07
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 21	-1.8 percentage points of LVEF	Standard Deviation 5.72
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 24	-0.7 percentage points of LVEF	Standard Deviation 4.03
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 27	0.0 percentage points of LVEF	Standard Deviation 2.83
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 30	-1.3 percentage points of LVEF	Standard Deviation 6.55
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 33	-0.5 percentage points of LVEF	Standard Deviation 3.21
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 36	0.0 percentage points of LVEF	Standard Deviation 2.9
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 39	-1.3 percentage points of LVEF	Standard Deviation 3.51
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 42	1.0 percentage points of LVEF	Standard Deviation 0
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 45	0.0 percentage points of LVEF	Standard Deviation 1.41
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 48	-2.0 percentage points of LVEF	Standard Deviation 2.83
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Cycle 51	-18.0 percentage points of LVEF	—
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at Safety Follow-Up	-4.3 percentage points of LVEF	Standard Deviation 12.98
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at 3 Month Follow-Up	-2.1 percentage points of LVEF	Standard Deviation 4.8
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at 6 Month Follow-Up	-1.8 percentage points of LVEF	Standard Deviation 4.41
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at 9 Month Follow-Up	-3.4 percentage points of LVEF	Standard Deviation 6.44
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at 12 Month Follow-Up	-2.3 percentage points of LVEF	Standard Deviation 4.4
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at 15 Month Follow-Up	-4.7 percentage points of LVEF	Standard Deviation 5.51
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at 18 Month Follow-Up	-10.0 percentage points of LVEF	Standard Deviation 7.07
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at 21 Month Follow-Up	-5.0 percentage points of LVEF	—
Pertuzumab in Combination With Trastuzumab and Docetaxel	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time	Change from BL at 24 Month Follow-Up	-5.0 percentage points of LVEF	—

Primary

Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time

Left ventricular ejection fraction (LVEF) assessments were performed within 42 days of enrollment and every three treatment cycles by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan; ECHO was the preferred method. In order to be eligible for this study, an LVEF greater than or equal to (≥)50% was required at screening. The same method of LVEF assessment for each participant must have been used throughout the study, and to the extent possible, have been obtained at the same institution. The following are definitions for the three categories of LVEF findings: 'Normal' was defined as LVEF ≥45%; 'Abnormal but not clinically significant' was defined as LVEF \<45% but not clinically significant in the investigator's judgment; 'Abnormal and clinically significant' was defined as LVEF \<45% and clinically significant in the investigator's judgment.

Population: Safety Population

Arm	Measure	Group	Category	Value (COUNT_OF_PARTICIPANTS)
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 18	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 21	Normal	10 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 21	Abnormal But Not Clinically Significant	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 21	Abnormal and Clinically Significant	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 24	Normal	8 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 24	Abnormal But Not Clinically Significant	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 24	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 27	Normal	5 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 27	Abnormal But Not Clinically Significant	2 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 27	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 30	Normal	3 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 30	Abnormal But Not Clinically Significant	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 30	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 33	Normal	5 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 33	Abnormal But Not Clinically Significant	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 33	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 36	Normal	5 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 36	Abnormal But Not Clinically Significant	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 36	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 39	Normal	2 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 39	Abnormal But Not Clinically Significant	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 39	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 42	Normal	2 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 42	Abnormal But Not Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 42	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 45	Normal	2 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 45	Abnormal But Not Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 45	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 48	Normal	2 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 48	Abnormal But Not Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 48	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 51	Normal	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 51	Abnormal But Not Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 51	Abnormal and Clinically Significant	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Safety Follow-Up	Normal	24 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Safety Follow-Up	Abnormal But Not Clinically Significant	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Safety Follow-Up	Abnormal and Clinically Significant	3 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	3 Month Follow-Up	Normal	17 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	3 Month Follow-Up	Abnormal But Not Clinically Significant	3 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	3 Month Follow-Up	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	6 Month Follow-Up	Normal	18 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	6 Month Follow-Up	Abnormal But Not Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	6 Month Follow-Up	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	9 Month Follow-Up	Normal	13 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	9 Month Follow-Up	Abnormal But Not Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	9 Month Follow-Up	Abnormal and Clinically Significant	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	12 Month Follow-Up	Normal	10 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	12 Month Follow-Up	Abnormal But Not Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	12 Month Follow-Up	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	15 Month Follow-Up	Normal	3 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	15 Month Follow-Up	Abnormal But Not Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	15 Month Follow-Up	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	18 Month Follow-Up	Normal	2 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	18 Month Follow-Up	Abnormal But Not Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	18 Month Follow-Up	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Baseline	Normal	50 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Baseline	Abnormal But Not Clinically Significant	2 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Baseline	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 3	Normal	48 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 3	Abnormal But Not Clinically Significant	3 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 3	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 6	Normal	37 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 6	Abnormal But Not Clinically Significant	3 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 6	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 9	Normal	24 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 9	Abnormal But Not Clinically Significant	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 9	Abnormal and Clinically Significant	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 12	Normal	17 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 12	Abnormal But Not Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 12	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 15	Normal	16 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 15	Abnormal But Not Clinically Significant	2 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 15	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 18	Normal	11 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	Cycle 18	Abnormal But Not Clinically Significant	2 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	21 Month Follow-Up	Normal	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	21 Month Follow-Up	Abnormal But Not Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	21 Month Follow-Up	Abnormal and Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	24 Month Follow-Up	Normal	1 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	24 Month Follow-Up	Abnormal But Not Clinically Significant	0 Participants
Pertuzumab in Combination With Trastuzumab and Docetaxel	Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time	24 Month Follow-Up	Abnormal and Clinically Significant	0 Participants

Primary

Number of Participants Who Died Due to a Serious Adverse Event by Cause of Death

The number of participants who died due to a serious adverse event was counted by the cause of death.