A Study of Pertuzumab in Combination With Trastuzumab Plus an Aromatase Inhibitor in Participants With Metastatic Human Epidermal Growth Factor Receptor 2 (HER2)-Positive and Hormone Receptor-Positive Advanced Breast Cancer (PERTAIN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT01491737

Recruitment Status : Completed

First Posted : December 14, 2011

Results First Posted : June 7, 2017

Last Update Posted : October 28, 2020

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Hoffmann-La Roche

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Breast Cancer
Interventions	Drug: Pertuzumab Drug: Trastuzumab Drug: Aromatase Inhibitor Drug: Induction Chemotherapy
Enrollment	258

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 258 participants were enrolled in the study.


Arm/Group Title	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy	Arm B: Trastuzumab + AI +/- Chemotherapy
Arm/Group Description	Participants received pertuzumab at...	Participants received trastuzumab a...
Arm/Group Description	Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.	Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Period Title: Overall Study
Started ^[1]	129	129
Received at Least One Dose of Study Drug ^[2]	127	124
Entered Follow-Up (Post-Treatment)	120	116
Completed	0	0
Not Completed	129	129
Reason Not Completed
Withdrawal by Subject	20	17
Lost to Follow-up	2	10
Death	63	57
Study Termination by Sponsor	36	36
Reason Not Specified	8	9
[1] Intent-to-Treat (ITT) Population [2] Safety Population

Baseline Characteristics

Arm/Group Title		Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy	Arm B: Trastuzumab + AI +/- Chemotherapy	Total
Arm/Group Description		Participants received pertuzumab at...	Participants received trastuzumab a...	Total of all reporting groups
Arm/Group Description		Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.	Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.	Total of all reporting groups
Overall Number of Baseline Participants		129	129	258
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Intent-to-Treat (ITT) population included all randomized participants.
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	129 participants	129 participants	258 participants
		60.9 (10.85)	62.3 (11.54)	61.6 (11.20)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	129 participants	129 participants	258 participants
	Female	129 100.0%	129 100.0%	258 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	129 participants	129 participants	258 participants
	American Indian or Alaska Native	0 0.0%	1 0.8%	1 0.4%
	Asian	10 7.8%	18 14.0%	28 10.9%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	4 3.1%	5 3.9%	9 3.5%
	White	104 80.6%	93 72.1%	197 76.4%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	11 8.5%	12 9.3%	23 8.9%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	129 participants	129 participants	258 participants
	Hispanic/Latino	45 34.9%	40 31.0%	85 32.9%
	Chinese	0 0.0%	0 0.0%	0 0.0%
	Indian (Indian subcontinent)	10 7.8%	16 12.4%	26 10.1%
	Japanese	0 0.0%	1 0.8%	1 0.4%
	Mixed Ethnicity	0 0.0%	0 0.0%	0 0.0%
	Other	63 48.8%	60 46.5%	123 47.7%
	Missing	11 8.5%	12 9.3%	23 8.9%
Number of Participants by Induction Chemotherapy and Prior Adjuvant Hormone Therapy ^[1] [2] Measure Type: Count of Participants Unit of measure: Participants
Induction Chemotherapy - Yes	Number Analyzed	75 participants	73 participants	148 participants
	<12 Months Since Hormone Therapy	12 16.0%	12 16.4%	24 16.2%
	≥12 Months Since Hormone Therapy	24 32.0%	23 31.5%	47 31.8%
	No Prior Hormone Therapy	39 52.0%	38 52.1%	77 52.0%
Induction Chemotherapy - No	Number Analyzed	54 participants	56 participants	110 participants
	<12 Months Since Hormone Therapy	12 22.2%	12 21.4%	24 21.8%
	≥12 Months Since Hormone Therapy	18 33.3%	19 33.9%	37 33.6%
	No Prior Hormone Therapy	24 44.4%	25 44.6%	49 44.5%
		[1] Measure Description: Participants were stratified at randomization according to the following factors: -Chosen to receive induction chemotherapy? (Yes vs. No); -Time since adjuvant hormone therapy (<12 months vs. ≥12 months), or no prior hormone therapy. [2] Measure Analysis Population Description: All 258 participants who were enrolled on this study are accounted for between the induction chemotherapy categories (yes vs. no).

Outcome Measures

1.Primary Outcome


Title	Progression-Free Survival (PFS)
Description	Progression-free survival (PFS) was defined as the time from randomiza...
Description	Progression-free survival (PFS) was defined as the time from randomization until the first radiographically documented progression of disease or death from any cause, whichever occurred first (either during study treatment or during follow-up). Progression of disease was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 and is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum of target lesion diameters must also demonstrate an absolute increase of at least 5 mm (Note: the appearance of one or more new lesions is also considered progression). Participants with no PFS events were censored at the time of the last evaluable tumor assessment. The primary analysis of PFS was planned to be performed when a total of 165 PFS events had occurred, and the final analysis after at least 60 months follow-up.
Time Frame	Median [full range] of follow-up time on study for: Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B; Final Analysis: 73.20 [0.03-88.34] months vs. 71.06 [0.03-88.97] months in Arm A vs. Arm B

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all randomized participants.


Arm/Group Title	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy	Arm B: Trastuzumab + AI +/- Chemotherapy
Arm/Group Description:	Participants received pertuzumab at...	Participants received trastuzumab a...
Arm/Group Description:	Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.	Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed	129	129
Median (95% Confidence Interval) Unit of Measure: months
Primary Analysis	18.89 (14.09 to 27.66)	15.80 (11.04 to 18.56)
Final Analysis	20.63 (14.39 to 28.35)	15.80 (11.04 to 18.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
	Comments	Primary Analysis. Log Rank tested the following: Null Hypothesis (H0): the distribution of the PFS time was the same in Arms A & B; The Alternative Hypothesis (H1): the distribution of the PFS time was different in Arms A & B. A Cox proportional hazards model tested the HR. If the HR of investigational arm (Arm A) compared with control arm (Arm B) with respect to PFS was assumed to be constant over time (λ) then the null (H0) and alternative hypotheses (H1) were: H0: λ =1; H1: λ ≠1.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0070
	Comments	Test was performed at 2-sided alpha of 5%.
	Method	Log Rank
	Comments	Stratified log-rank test based upon Kaplan-Meier including induction chemotherapy and prior adjuvant hormone therapy stratification factors.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95% 0.48 to 0.89
	Estimation Comments	Hazard ratio comparing Arm A vs. B from stratified Cox proportional hazards model including stratification factors.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
	Comments	Final Analysis
	Type of Statistical Test	Other
	Comments	Exploratory

Statistical Test of Hypothesis	P-Value	0.0059
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified log-rank test based upon Kaplan-Meier including induction chemotherapy and prior adjuvant hormone therapy stratification factors.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95% 0.50 to 0.89
	Estimation Comments	Hazard ratio comparing Arm A vs. B from stratified Cox proportional hazards model including stratification factors.

2.Secondary Outcome


Title	Overall Survival (OS)
Description	Overall survival (OS) was defined as the time from the date of randomi...
Description	Overall survival (OS) was defined as the time from the date of randomization to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis 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 (pertuzumab, trastuzumab, AI or induction chemotherapy), and participants with no post-baseline information were censored at the date of randomization. The primary analysis of OS was planned to be performed at the same time as for PFS (when a total of 165 PFS events had occurred), and the final analysis was planned after at least 60 months follow-up for all participants.
Time Frame	Median [full range] of follow-up time on study for: Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B; Final Analysis: 73.20 [0.03-88.34] months vs. 71.06 [0.03-88.97] months in Arm A vs. Arm B

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants.


Arm/Group Title	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy	Arm B: Trastuzumab + AI +/- Chemotherapy
Arm/Group Description:	Participants received pertuzumab at...	Participants received trastuzumab a...
Arm/Group Description:	Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.	Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed	129	129
Median (95% Confidence Interval) Unit of Measure: Months
Primary Analysis	NA ^[1] (NA to NA)	NA ^[2] (41.40 to NA)
Final Analysis	60.16 (47.21 to 79.01)	57.17 ^[3] (45.44 to NA)

[1]

Median and lower and upper limits of the 95% confidence interval were not reached because not enough events had occurred at the time of analysis.

[2]

Median and upper limit of the 95% confidence interval were not reached because not enough events had occurred at the time of analysis.

[3]

Upper limit of 95% confidence interval was not reached because not enough events had occurred the time of analysis.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
	Comments	Primary Analysis. This study was not powered for overall survival (OS), so adequately powered statistical testing for this outcome measure was not possible.
	Type of Statistical Test	Other
	Comments	Exploratory

Statistical Test of Hypothesis	P-Value	0.5850
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified log-rank test based upon Kaplan-Meier including induction chemotherapy and prior adjuvant hormone therapy stratification factors.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95% 0.69 to 1.91
	Estimation Comments	Hazard ratio comparing Arm A vs. B from stratified Cox proportional hazards model including stratification factors.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
	Comments	Final Analysis. This study was not powered for overall survival (OS), so adequately powered statistical testing for this outcome measure was not possible.
	Type of Statistical Test	Other
	Comments	Exploratory

Statistical Test of Hypothesis	P-Value	0.7833
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified log-rank test based upon Kaplan-Meier including induction chemotherapy and prior adjuvant hormone therapy stratification factors.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95% 0.73 to 1.52
	Estimation Comments	Hazard ratio comparing Arm A vs. B from stratified Cox proportional hazards model including stratification factors.

3.Secondary Outcome


Title	Overall Response Rate (ORR)
Description	The overall response rate (ORR) was defined as the percentage of parti...
Description	The overall response rate (ORR) was defined as the percentage of participants with best (confirmed) overall response (BOR) of either complete response (CR) or partial response (PR) from start of study treatment until progressive disease (PD)/recurrence or death, as assessed by the investigator according to RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference baseline sum diameters; stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Participants needed to have two consecutive assessments of PR or CR at least 4 weeks apart to be a responder. Analysis of this outcome measure was only planned to occur at the time of primary analysis.
Time Frame	Median [full range] of follow-up time on study for Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Only participants with measurable disease at baseline were included in the analysis.


Arm/Group Title	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy	Arm B: Trastuzumab + AI +/- Chemotherapy
Arm/Group Description:	Participants received pertuzumab at...	Participants received trastuzumab a...
Arm/Group Description:	Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.	Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed	109	106
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
ORR (CR + PR)	63.3 (53.5 to 72.3)	55.7 (45.7 to 65.3)
Non-responders (SD + PD + NE)	36.7 (27.7 to 46.5)	44.3 (34.7 to 54.3)
Complete Response (CR)	7.3 (3.2 to 14.0)	0.9 (0.0 to 5.1)
Partial Response (PR)	56.0 (46.1 to 65.5)	54.7 (44.8 to 64.4)
Stable Disease (SD)	26.6 (18.6 to 35.9)	27.4 (19.1 to 36.9)
Progressive Disease (PD)	5.5 (2.0 to 11.6)	12.3 (6.7 to 20.1)
Not Evaluable (NE)	4.5 (1.5 to 10.4)	4.7 (1.5 to 10.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
	Comments	ORR for Arm A vs Arm B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.2537
	Comments	Test was performed at 2-sided alpha of 5%. There was no multiplicity adjustment.
	Method	Chi-squared
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in ORR
	Estimated Value	7.6
	Confidence Interval	(2-Sided) 95% -6.0 to 21.3
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Clinical Benefit Rate (CBR)
Description	Clinical Benefit Rate (CBR) was defined as the percentage of participa...
Description	Clinical Benefit Rate (CBR) was defined as the percentage of participants with best (confirmed) partial response (PR) or complete response (CR) or stable disease (SD) for at least 6 months. According to RECIST version 1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Analysis of this outcome measure was only planned to occur at the time of primary analysis.
Time Frame	Median [full range] of follow-up time on study for Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Only participants with measurable disease at baseline were included in the analysis.


Arm/Group Title	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy	Arm B: Trastuzumab + AI +/- Chemotherapy
Arm/Group Description:	Participants received pertuzumab at...	Participants received trastuzumab a...
Arm/Group Description:	Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.	Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed	109	106
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
CBR (CR + PR + SD for ≥6 Months)	68.8 (59.2 to 77.3)	67.0 (57.2 to 75.8)
Complete Response (CR)	7.3 (3.2 to 14.0)	0.9 (0.0 to 5.1)
Partial Response (PR)	56.0 (46.1 to 65.5)	54.7 (44.8 to 64.4)
Stable Disease (SD) for ≥6 Months	5.5 (2.0 to 11.6)	11.3 (6.0 to 18.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
	Comments	CBR for Arm A vs. Arm B
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.7743
	Comments	Test was performed at 2-sided alpha of 5%. There was no multiplicity adjustment.
	Method	Chi-squared
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in CBR
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95% -11.2 to 14.8
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Duration of Response (DOR)
Description	Duration of response (DOR) was defined as the period from the date of ...
Description	Duration of response (DOR) was defined as the period from the date of initial confirmed partial response (PR) or complete response (CR) until the date of progressive disease or death from any cause. According to RECIST version 1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants with no documented progression after CR or PR were censored at the last date at which they were known to have had the CR or PR, respectively. The primary analysis of DOR was planned to be performed at the same time as for PFS (when a total of 165 PFS events had occurred), and the final analysis was planned after at least 60 months follow-up for all participants.
Time Frame	Median [full range] of follow-up time on study for: Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B; Final Analysis: 73.20 [0.03-88.34] months vs. 71.06 [0.03-88.97] months in Arm A vs. Arm B

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Only participants who had measurable disease at baseline and were responders (CR or PR) were included in this analysis.


Arm/Group Title		Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy	Arm B: Trastuzumab + AI +/- Chemotherapy
Arm/Group Description:		Participants received pertuzumab at...	Participants received trastuzumab a...
Arm/Group Description:		Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.	Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed		69	61
Median (95% Confidence Interval) Unit of Measure: months
Primary Analysis	Number Analyzed	69 participants	59 participants
Primary Analysis		27.10 ^[1] (14.13 to NA)	15.11 (12.09 to 20.96)
Final Analysis	Number Analyzed	69 participants	61 participants
Final Analysis		27.40 (15.24 to 44.35)	16.36 (12.09 to 20.96)

[1]

Upper limit of the 95% confidence interval was not reached because not enough events had occurred at the time of analysis.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
	Comments	Primary Analysis. Log Rank tested the following: Null Hypothesis (H0): the distribution of the DOR time was the same in Arms A & B; The Alternative Hypothesis (H1): the distribution of the DOR time was different in Arms A & B. A Cox proportional hazards model tested the HR. If the HR of investigational arm (Arm A) compared with control arm (Arm B) with respect to DOR was assumed to be constant over time (λ) then the null (H0) and alternative hypotheses (H1) were: H0: λ =1; H1: λ ≠1.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0181
	Comments	Test was performed at 2-sided alpha of 5%.
	Method	Log Rank
	Comments	Log-rank test from unstratified analysis based upon Kaplan-Meier approach. There was no multiplicity adjustment.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95% 0.36 to 0.91
	Estimation Comments	Hazard ratio from stratified Cox proportional hazards model including stratification factors of induction chemotherapy and prior adjuvant hormone therapy.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
	Comments	Final Analysis.
	Type of Statistical Test	Other
	Comments	Exploratory

Statistical Test of Hypothesis	P-Value	0.0205
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Log-rank test from unstratified analysis based upon Kaplan-Meier approach. There was no multiplicity adjustment.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95% 0.41 to 0.93
	Estimation Comments	Hazard ratio from stratified Cox proportional hazards model including stratification factors of induction chemotherapy and prior adjuvant hormone therapy.

6.Secondary Outcome


Title	Time to Response (TTR)
Description	Time to Response (TTR) was defined as the time from the date of random...
Description	Time to Response (TTR) was defined as the time from the date of randomization to the date of first complete response (CR) or partial response (PR). According to RECIST version 1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For participants who did not have a confirmed response, a censored TTR was calculated at the date of the last adequate tumor assessment. If no tumor assessment is performed for the participant (or all post-baseline assessments are not evaluable or PD) the censoring day would be set to day 1 (date of randomization). Analysis of this outcome measure was only planned to occur at the time of primary analysis.
Time Frame	Median [full range] of follow-up time on study for Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Only participants with measurable disease at baseline were included in this analysis.


Arm/Group Title	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy	Arm B: Trastuzumab + AI +/- Chemotherapy
Arm/Group Description:	Participants received pertuzumab at...	Participants received trastuzumab a...
Arm/Group Description:	Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.	Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed	109	106
Median (95% Confidence Interval) Unit of Measure: months
	2.53 (2.10 to 4.37)	3.91 (2.10 to 4.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
	Comments	Log Rank tested the following: Null Hypothesis (H0): the distribution of the TTR time was the same in Arms A & B; The Alternative Hypothesis (H1): the distribution of the TTR time was different in Arms A & B. A Cox proportional hazards model tested the HR. If the HR of investigational arm (Arm A) compared with control arm (Arm B) with respect to TTR was assumed to be constant over time (λ) then the null (H0) and alternative hypotheses (H1) were: H0: λ =1; H1: λ ≠1.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.5597
	Comments	Test was performed at 2-sided alpha of 5%.
	Method	Log Rank
	Comments	The log-rank test from unstratified analysis was based upon Kaplan-Meier approach. There was no multiplicity adjustment.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95% 0.78 to 1.57
	Estimation Comments	Hazard ratio from stratified Cox proportional hazards model including the induction chemotherapy and prior adjuvant hormone therapy stratification factors.

7.Secondary Outcome


Title	Change From Baseline in Health-Related Quality of Life as Determined by European Quality of Life 5-Dimension (EQ-5D) Visual Analog Scale (VAS) Scores
Description	The EQ-5D VAS is a participant-rated questionnaire to assess health-re...
Description	The EQ-5D VAS is a participant-rated questionnaire to assess health-related quality of life (QoL) in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state.
Time Frame	Baseline and every 3 cycles until treatment discontinuation (up to Cycle 120; 1 cycle is 21 days)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. The number analyzed only included those who had a non-missing assessment for a specified time point.


Arm/Group Title		Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy	Arm B: Trastuzumab + AI +/- Chemotherapy
Arm/Group Description:		Participants received pertuzumab at...	Participants received trastuzumab a...
Arm/Group Description:		Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.	Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed		129	129
Mean (Standard Deviation) Unit of Measure: unit on a scale
Baseline (BL) - Value at Visit	Number Analyzed	98 participants	101 participants
Baseline (BL) - Value at Visit		73.0 (19.34)	72.8 (18.83)
Change from BL at Cycle 3	Number Analyzed	87 participants	87 participants
Change from BL at Cycle 3		3.3 (14.90)	1.9 (15.67)
Change from BL at Cycle 6	Number Analyzed	82 participants	75 participants
Change from BL at Cycle 6		3.5 (18.91)	0.5 (13.63)
Change from BL at Cycle 9	Number Analyzed	68 participants	66 participants
Change from BL at Cycle 9		5.3 (18.80)	2.1 (15.20)
Change from BL at Cycle 12	Number Analyzed	58 participants	52 participants
Change from BL at Cycle 12		10.7 (17.91)	4.0 (15.34)
Change from BL at Cycle 15	Number Analyzed	54 participants	50 participants
Change from BL at Cycle 15		9.1 (17.25)	1.4 (22.16)
Change from BL at Cycle 18	Number Analyzed	47 participants	43 participants
Change from BL at Cycle 18		7.5 (12.85)	3.5 (15.76)
Change from BL at Cycle 21	Number Analyzed	44 participants	39 participants
Change from BL at Cycle 21		5.8 (13.68)	3.5 (19.70)
Change from BL at Cycle 24	Number Analyzed	39 participants	38 participants
Change from BL at Cycle 24		6.2 (14.30)	3.2 (16.66)
Change from BL at Cycle 27	Number Analyzed	35 participants	34 participants
Change from BL at Cycle 27		7.5 (14.01)	3.9 (22.00)
Change from BL at Cycle 30	Number Analyzed	33 participants	29 participants
Change from BL at Cycle 30		8.3 (14.25)	4.9 (16.98)
Change from BL at Cycle 33	Number Analyzed	34 participants	24 participants
Change from BL at Cycle 33		5.1 (14.70)	4.3 (15.59)
Change from BL at Cycle 36	Number Analyzed	30 participants	21 participants
Change from BL at Cycle 36		7.3 (15.19)	5.9 (15.13)
Change from BL at Cycle 39	Number Analyzed	30 participants	18 participants
Change from BL at Cycle 39		8.1 (16.33)	2.4 (29.68)
Change from BL at Cycle 42	Number Analyzed	25 participants	15 participants
Change from BL at Cycle 42		6.4 (19.18)	9.0 (17.55)
Change from BL at Cycle 45	Number Analyzed	22 participants	14 participants
Change from BL at Cycle 45		9.7 (15.01)	9.9 (19.52)
Change from BL at Cycle 48	Number Analyzed	19 participants	13 participants
Change from BL at Cycle 48		8.8 (12.50)	6.8 (17.22)
Change from BL at Cycle 51	Number Analyzed	18 participants	13 participants
Change from BL at Cycle 51		7.2 (14.81)	9.1 (19.11)
Change from BL at Cycle 54	Number Analyzed	16 participants	12 participants
Change from BL at Cycle 54		4.7 (23.48)	7.6 (17.85)
Change from BL at Cycle 57	Number Analyzed	16 participants	11 participants
Change from BL at Cycle 57		6.8 (18.08)	10.5 (16.81)
Change from BL at Cycle 60	Number Analyzed	16 participants	11 participants
Change from BL at Cycle 60		8.2 (15.88)	10.9 (18.27)
Change from BL at Cycle 63	Number Analyzed	16 participants	10 participants
Change from BL at Cycle 63		4.0 (20.88)	8.8 (14.64)
Change from BL at Cycle 66	Number Analyzed	14 participants	8 participants
Change from BL at Cycle 66		10.4 (16.92)	4.1 (15.69)
Change from BL at Cycle 69	Number Analyzed	13 participants	7 participants
Change from BL at Cycle 69		7.5 (17.35)	5.0 (16.77)
Change from BL at Cycle 72	Number Analyzed	13 participants	8 participants
Change from BL at Cycle 72		6.2 (16.10)	5.8 (16.10)
Change from BL at Cycle 75	Number Analyzed	11 participants	7 participants
Change from BL at Cycle 75		8.6 (19.12)	5.1 (15.50)
Change from BL at Cycle 78	Number Analyzed	11 participants	7 participants
Change from BL at Cycle 78		12.8 (17.45)	6.9 (14.58)
Change from BL at Cycle 81	Number Analyzed	11 participants	6 participants
Change from BL at Cycle 81		11.5 (18.39)	8.0 (14.76)
Change from BL at Cycle 84	Number Analyzed	11 participants	6 participants
Change from BL at Cycle 84		11.2 (19.71)	1.3 (18.13)
Change from BL at Cycle 87	Number Analyzed	11 participants	4 participants
Change from BL at Cycle 87		11.2 (18.17)	-3.0 (11.22)
Change from BL at Cycle 90	Number Analyzed	11 participants	4 participants
Change from BL at Cycle 90		10.9 (18.28)	-3.0 (12.36)
Change from BL at Cycle 93	Number Analyzed	11 participants	5 participants
Change from BL at Cycle 93		7.1 (15.43)	6.6 (13.89)
Change from BL at Cycle 96	Number Analyzed	8 participants	5 participants
Change from BL at Cycle 96		7.5 (16.04)	8.6 (12.64)
Change from BL at Cycle 99	Number Analyzed	9 participants	5 participants
Change from BL at Cycle 99		4.4 (17.22)	5.6 (16.71)
Change from BL at Cycle 102	Number Analyzed	8 participants	3 participants
Change from BL at Cycle 102		5.6 (16.35)	10.0 (17.32)
Change from BL at Cycle 105	Number Analyzed	8 participants	1 participants
Change from BL at Cycle 105		4.4 (16.35)	0.0 ^[1] (NA)
Change from BL at Cycle 108	Number Analyzed	7 participants	1 participants
Change from BL at Cycle 108		4.0 (14.39)	0.0 ^[1] (NA)
Change from BL at Cycle 111	Number Analyzed	4 participants	0 participants
Change from BL at Cycle 111		3.3 (21.50)
Change from BL at Cycle 114	Number Analyzed	4 participants	0 participants
Change from BL at Cycle 114		-1.3 (17.97)
Change from BL at Cycle 117	Number Analyzed	1 participants	0 participants
Change from BL at Cycle 117		-5.0 ^[1] (NA)
Change from BL at Cycle 120	Number Analyzed	1 participants	0 participants
Change from BL at Cycle 120		-5.0 ^[1] (NA)

[1]

Standard deviation could not be calculated using data from a single participant.

8.Secondary Outcome


Title	Overview of the Number of Participants With Adverse Events, Severity Determined According to NCI-CTCAE Version 4.03
Description	All adverse events (AEs) occurring during the study and until the post...
Description	All adverse events (AEs) occurring during the study and until the post-treatment safety follow-up visit approximately 28 days after last study medication were recorded; thereafter, only study drug-related serious adverse events (SAEs) continued to be collected. The investigator graded all AEs for severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. AEs suggestive of congestive heart failure (CHF) were identified by the SMQ (wide) "Cardiac Failure" with a status of "serious", which included the preferred terms cardiac failure, left ventricular dysfunction, and pulmonary oedema.
Time Frame	From Baseline until the end of post-treatment follow-up (up to 89 months)

Outcome Measure Data

Analysis Population Description

Safety population: included all participants who had received at least 1 dose of any study medication assigned to treatment arms as treated.


Arm/Group Title		Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy	Arm B: Trastuzumab + AI +/- Chemotherapy
Arm/Group Description:		Participants received pertuzumab at...	Participants received trastuzumab a...
Arm/Group Description:		Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.	Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed		127	124
Measure Type: Count of Participants Unit of Measure: Participants
Any Adverse Event (AE)	Number Analyzed	127 participants	124 participants
Any Adverse Event (AE)		122 96.1%	122 98.4%
Any AE, Grade ≥3	Number Analyzed	127 participants	124 participants
Any AE, Grade ≥3		72 56.7%	51 41.1%
Any Serious Adverse Event (SAE), Grade ≥3	Number Analyzed	127 participants	124 participants
Any Serious Adverse Event (SAE), Grade ≥3		35 27.6%	22 17.7%
Any AE, Grade 5	Number Analyzed	127 participants	124 participants
Any AE, Grade 5		1 0.8%	1 0.8%
Any SAE	Number Analyzed	127 participants	124 participants
Any SAE		46 36.2%	28 22.6%
SAE Related to Pertuzumab	Number Analyzed	127 participants	124 participants
SAE Related to Pertuzumab		10 7.9%	NA ^[1]
SAE Related to Trastuzumab	Number Analyzed	127 participants	124 participants
SAE Related to Trastuzumab		9 7.1%	2 1.6%
SAE Related to Docetaxel	Number Analyzed	74 participants	69 participants
SAE Related to Docetaxel		6 8.1%	4 5.8%
SAE Related to Paclitaxel	Number Analyzed	74 participants	69 participants
SAE Related to Paclitaxel		3 4.1%	0 0.0%
Any AE Leading to Discontinuation of Any Treatment	Number Analyzed	127 participants	124 participants
Any AE Leading to Discontinuation of Any Treatment		20 15.7%	10 8.1%
Any AE Leading to Pertuzumab Discontinuation	Number Analyzed	127 participants	124 participants
Any AE Leading to Pertuzumab Discontinuation		16 12.6%	NA ^[1]
Any AE Leading to Trastuzumab Discontinuation	Number Analyzed	127 participants	124 participants
Any AE Leading to Trastuzumab Discontinuation		16 12.6%	6 4.8%
Any AE Leading to Interruption of Any Treatment	Number Analyzed	127 participants	124 participants
Any AE Leading to Interruption of Any Treatment		59 46.5%	26 21.0%
Any AE Leading to Pertuzumab Interruption	Number Analyzed	127 participants	124 participants
Any AE Leading to Pertuzumab Interruption		44 34.6%	NA ^[1]
Any AE Leading to Trastuzumab Interruption	Number Analyzed	127 participants	124 participants
Any AE Leading to Trastuzumab Interruption		48 37.8%	16 12.9%
Any AE Related to Pertuzumab	Number Analyzed	127 participants	124 participants
Any AE Related to Pertuzumab		82 64.6%	NA ^[1]
Any AE Related to Trastuzumab	Number Analyzed	127 participants	124 participants
Any AE Related to Trastuzumab		81 63.8%	62 50.0%
AE Suggestive of Congestive Heart Failure	Number Analyzed	127 participants	124 participants
AE Suggestive of Congestive Heart Failure		5 3.9%	1 0.8%

[1]

None of the participants in Arm B were treated with pertuzumab.

9.Secondary Outcome


Title	Number of Participants Who Died Over the Course of the Study by Reported Cause of Death and Time of Death Relative to First or Last Dose of Study Treatment
Description	The causes of death over the course of the study, regardless of whethe...
Description	The causes of death over the course of the study, regardless of whether the death was related to study treatment, are listed by preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA), version 22.1.
Time Frame	From Baseline until the end of post-treatment follow-up (up to 89 months)

Outcome Measure Data

Analysis Population Description

Safety Population: included all participants who had received at least 1 dose of any study medication assigned to treatment arms as treated.


Arm/Group Title	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy	Arm B: Trastuzumab + AI +/- Chemotherapy
Arm/Group Description:	Participants received pertuzumab at...	Participants received trastuzumab a...
Arm/Group Description:	Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.	Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed	127	124
Measure Type: Count of Participants Unit of Measure: Participants
Total Number of Deaths	62 48.8%	57 46.0%
Deaths Related to Any Study Treatment	0 0.0%	0 0.0%
Cause of Death: Cardiac Arrest	1 0.8%	0 0.0%
Cause of Death: Craniocerebral Injury	1 0.8%	0 0.0%
Cause of Death: Dyspnoea	1 0.8%	0 0.0%
Cause of Death: High-grade B-cell Lymphoma	1 0.8%	0 0.0%
Cause of Death: Sudden Death	0 0.0%	1 0.8%
Cause of Death: Unevaluable Event	2 1.6%	1 0.8%
Cause of Death: Progressive Disease	56 44.1%	55 44.4%
Total Deaths Within 30 Days After First Dose	0 0.0%	0 0.0%
Total Deaths Within 28 Days After Last Dose	1 0.8%	2 1.6%
Total Deaths Within 60 Days After Last Dose	2 1.6%	4 3.2%

10.Secondary Outcome


Title	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Values Over the Course of the Study
Description	Left ventricular ejection fraction (LVEF) is the measurement of how mu...
Description	Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. A normal LVEF ranges from 55% to 70%, as measured by echocardiogram or multiple-gated acquisition (MUGA) scan. All participants must have had a baseline LVEF of at least (≥)50% to enroll in the study; patients with clinically significant cardiovascular disease or baseline LVEF below 50% were not eligible for this study.
Time Frame	Baseline and every 3 cycles until treatment discontinuation (up to Cycle 120; 1 cycle is 21 days)

Outcome Measure Data

Analysis Population Description

Safety Population: included all participants who had received at least 1 dose of any study medication assigned to treatment arms as treated.


Arm/Group Title		Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy	Arm B: Trastuzumab + AI +/- Chemotherapy
Arm/Group Description:		Participants received pertuzumab at...	Participants received trastuzumab a...
Arm/Group Description:		Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.	Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed		127	124
Mean (Standard Deviation) Unit of Measure: Percentage points of LVEF
Baseline (BL) - Absolute LVEF at Visit	Number Analyzed	127 participants	123 participants
Baseline (BL) - Absolute LVEF at Visit		63.8 (6.23)	63.9 (6.12)
Change from BL at Cycle 3	Number Analyzed	114 participants	114 participants
Change from BL at Cycle 3		-1.0 (6.25)	-1.4 (6.23)
Change from BL at Cycle 6	Number Analyzed	101 participants	101 participants
Change from BL at Cycle 6		-2.3 (6.66)	-1.3 (6.03)
Change from BL at Cycle 9	Number Analyzed	87 participants	84 participants
Change from BL at Cycle 9		-2.5 (6.80)	-2.2 (6.52)
Change from BL at Cycle 12	Number Analyzed	75 participants	69 participants
Change from BL at Cycle 12		-2.4 (8.05)	-2.8 (6.99)
Change from BL at Cycle 15	Number Analyzed	64 participants	61 participants
Change from BL at Cycle 15		-2.9 (8.67)	-2.5 (6.94)
Change from BL at Cycle 18	Number Analyzed	62 participants	54 participants
Change from BL at Cycle 18		-1.9 (6.42)	-1.3 (6.19)
Change from BL at Cycle 21	Number Analyzed	53 participants	48 participants
Change from BL at Cycle 21		-1.1 (6.01)	-1.1 (6.64)
Change from BL at Cycle 24	Number Analyzed	52 participants	46 participants
Change from BL at Cycle 24		-2.1 (6.82)	-0.6 (6.19)
Change from BL at Cycle 27	Number Analyzed	46 participants	39 participants
Change from BL at Cycle 27		-1.6 (5.05)	-1.3 (5.87)
Change from BL at Cycle 30	Number Analyzed	43 participants	34 participants
Change from BL at Cycle 30		-1.4 (5.20)	-0.3 (6.03)
Change from BL at Cycle 33	Number Analyzed	44 participants	28 participants
Change from BL at Cycle 33		-2.8 (5.60)	1.2 (6.71)
Change from BL at Cycle 36	Number Analyzed	37 participants	24 participants
Change from BL at Cycle 36		-2.5 (5.50)	-0.2 (5.41)
Change from BL at Cycle 39	Number Analyzed	38 participants	23 participants
Change from BL at Cycle 39		-2.6 (5.72)	1.4 (4.87)
Change from BL at Cycle 42	Number Analyzed	35 participants	18 participants
Change from BL at Cycle 42		-2.1 (5.91)	1.9 (6.12)
Change from BL at Cycle 45	Number Analyzed	31 participants	17 participants
Change from BL at Cycle 45		-1.0 (5.54)	3.0 (5.27)
Change from BL at Cycle 48	Number Analyzed	28 participants	18 participants
Change from BL at Cycle 48		-3.3 (6.56)	-0.2 (7.50)
Change from BL at Cycle 51	Number Analyzed	27 participants	18 participants
Change from BL at Cycle 51		-1.4 (5.82)	1.0 (4.19)
Change from BL at Cycle 54	Number Analyzed	26 participants	13 participants
Change from BL at Cycle 54		-1.3 (6.17)	-1.0 (6.23)
Change from BL at Cycle 57	Number Analyzed	26 participants	15 participants
Change from BL at Cycle 57		-1.7 (6.43)	0.8 (5.68)
Change from BL at Cycle 60	Number Analyzed	25 participants	14 participants
Change from BL at Cycle 60		-2.5 (5.54)	-0.9 (3.91)
Change from BL at Cycle 63	Number Analyzed	26 participants	14 participants
Change from BL at Cycle 63		-2.1 (6.10)	0.8 (5.99)
Change from BL at Cycle 66	Number Analyzed	22 participants	13 participants
Change from BL at Cycle 66		-2.9 (7.80)	-0.4 (5.17)
Change from BL at Cycle 69	Number Analyzed	19 participants	9 participants
Change from BL at Cycle 69		-2.1 (7.23)	-1.5 (7.68)
Change from BL at Cycle 72	Number Analyzed	18 participants	12 participants
Change from BL at Cycle 72		-3.0 (4.97)	-1.0 (5.75)
Change from BL at Cycle 75	Number Analyzed	17 participants	12 participants
Change from BL at Cycle 75		-3.3 (6.59)	-1.1 (6.97)
Change from BL at Cycle 78	Number Analyzed	17 participants	9 participants
Change from BL at Cycle 78		-3.3 (5.58)	-1.1 (7.82)
Change from BL at Cycle 81	Number Analyzed	17 participants	9 participants
Change from BL at Cycle 81		-2.9 (6.83)	-2.6 (6.00)
Change from BL at Cycle 84	Number Analyzed	15 participants	9 participants
Change from BL at Cycle 84		-2.5 (7.66)	-4.5 (3.59)
Change from BL at Cycle 87	Number Analyzed	15 participants	8 participants
Change from BL at Cycle 87		-3.8 (5.76)	-1.4 (5.12)
Change from BL at Cycle 90	Number Analyzed	16 participants	7 participants
Change from BL at Cycle 90		-2.4 (7.69)	0.4 (6.77)
Change from BL at Cycle 93	Number Analyzed	14 participants	7 participants
Change from BL at Cycle 93		-1.8 (6.57)	-3.9 (6.00)
Change from BL at Cycle 96	Number Analyzed	12 participants	7 participants
Change from BL at Cycle 96		-0.7 (7.45)	-3.2 (5.50)
Change from BL at Cycle 99	Number Analyzed	11 participants	7 participants
Change from BL at Cycle 99		-3.4 (5.78)	-2.8 (8.41)
Change from BL at Cycle 102	Number Analyzed	13 participants	5 participants
Change from BL at Cycle 102		-1.3 (6.12)	-1.6 (9.68)
Change from BL at Cycle 105	Number Analyzed	12 participants	3 participants
Change from BL at Cycle 105		-0.4 (7.05)	-2.0 (12.17)
Change from BL at Cycle 108	Number Analyzed	9 participants	3 participants
Change from BL at Cycle 108		-3.4 (5.32)	-3.3 (8.33)
Change from BL at Cycle 111	Number Analyzed	4 participants	1 participants
Change from BL at Cycle 111		-6.3 (5.91)	-5.5 ^[1] (NA)
Change from BL at Cycle 114	Number Analyzed	4 participants	1 participants
Change from BL at Cycle 114		-4.0 (5.35)	-1.4 ^[1] (NA)
Change from BL at Cycle 117	Number Analyzed	1 participants	0 participants
Change from BL at Cycle 117		-11.0 ^[1] (NA)
Change from BL at Cycle 120	Number Analyzed	1 participants	0 participants
Change from BL at Cycle 120		-11.0 ^[1] (NA)

[1]

Standard deviation could not be calculated with data from a single participant.

Adverse Events

Time Frame	From Baseline until end of post-treatment follow-up (up to 89 months)
Adverse Event Reporting Description	All adverse events that occurred during the study and until the post-treatment safety follow-up visit approximately 28 days after last study medication were to be recorded. Thereafter, only serious adverse events thought to be related to study drug were collected.

Arm/Group Title	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy		Arm B: Trastuzumab + AI +/- Chemotherapy
Arm/Group Description	Participants received pertuzumab at...		Participants received trastuzumab a...
Arm/Group Description	Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.		Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
All-Cause Mortality
	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy		Arm B: Trastuzumab + AI +/- Chemotherapy
	Affected / at Risk (%)		Affected / at Risk (%)
Total	63/129 (48.84%)		57/129 (44.19%)
Serious Adverse Events Serious Adverse Events
	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy		Arm B: Trastuzumab + AI +/- Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/127 (36.22%)		28/124 (22.58%)
Blood and lymphatic system disorders
Febrile neutropenia ^† 1	4/127 (3.15%)	4	2/124 (1.61%)	2
Neutropenia ^† 1	1/127 (0.79%)	1	1/124 (0.81%)	1
Cardiac disorders
Atrial fibrillation ^† 1	2/127 (1.57%)	3	0/124 (0.00%)	0
Cardiac failure ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Left ventricular dysfunction ^† 1	4/127 (3.15%)	4	0/124 (0.00%)	0
Mitral valve disease ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Myocardial ischaemia ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Sinus tachycardia ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Myocardial infarction ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Endocrine disorders
Adrenal haemorrhage ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Gastrointestinal disorders
Abdominal distension ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Abdominal pain ^† 1	1/127 (0.79%)	1	1/124 (0.81%)	1
Constipation ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Diarrhoea ^† 1	2/127 (1.57%)	2	1/124 (0.81%)	1
Vomiting ^† 1	2/127 (1.57%)	3	1/124 (0.81%)	1
Large intestinal obstruction ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
General disorders
Chest pain ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Pyrexia ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Sudden death ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Hepatobiliary disorders
Cholecystitis ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Immune system disorders
Anaphylactic shock ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Contrast media allergy ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Hypersensitivity ^† 1	3/127 (2.36%)	3	0/124 (0.00%)	0
Infections and infestations
Abscess ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Colonic abscess ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Device related infection ^† 1	0/127 (0.00%)	0	2/124 (1.61%)	2
Erysipelas ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Escherichia urinary tract infection ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	2
Gastroenteritis ^† 1	3/127 (2.36%)	3	0/124 (0.00%)	0
Gastroenteritis viral ^† 1	1/127 (0.79%)	1	1/124 (0.81%)	1
Infection ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Mastitis ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Neutropenic sepsis ^† 1	1/127 (0.79%)	1	1/124 (0.81%)	1
Pneumonia ^† 1	6/127 (4.72%)	7	1/124 (0.81%)	1
Respiratory tract infection ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Sepsis ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Tooth infection ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Vascular device infection ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Injury, poisoning and procedural complications
Femoral neck fracture ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Fracture ^† 1	1/127 (0.79%)	1	1/124 (0.81%)	1
Humerus fracture ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Post procedural haematoma ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Spinal fracture ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Fall ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Metabolism and nutrition disorders
Hyperglycaemia ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Hyperuricaemia ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Hyponatraemia ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Dehydration ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Musculoskeletal and connective tissue disorders
Back pain ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Pain in extremity ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Pathological fracture ^† 1	1/127 (0.79%)	1	1/124 (0.81%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Adenoid cystic carcinoma of salivary gland ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
High-grade B-cell lymphoma ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Cancer pain ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Lung neoplasm ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Transitional cell carcinoma ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Tumour exudation ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Nervous system disorders
Hypoglycaemic coma ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Spinal cord compression ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Psychiatric disorders
Depression ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Confusional state ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Respiratory, thoracic and mediastinal disorders
Asthma ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Chronic obstructive pulmonary disease ^† 1	2/127 (1.57%)	2	0/124 (0.00%)	0
Dyspnoea ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Pleural effusion ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Pneumonitis ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Pulmonary embolism ^† 1	1/127 (0.79%)	1	1/124 (0.81%)	1
Pulmonary oedema ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Painful respiration ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
Surgical and medical procedures
Colostomy closure ^† 1	0/127 (0.00%)	0	1/124 (0.81%)	1
Vascular disorders
Haematoma ^† 1	1/127 (0.79%)	1	0/124 (0.00%)	0
1 Term from vocabulary, MedDRA version 22.1 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy		Arm B: Trastuzumab + AI +/- Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	120/127 (94.49%)		116/124 (93.55%)
Blood and lymphatic system disorders
Anaemia ^† 1	28/127 (22.05%)	53	18/124 (14.52%)	30
Neutropenia ^† 1	11/127 (8.66%)	14	13/124 (10.48%)	23
Eye disorders
Lacrimation increased ^† 1	9/127 (7.09%)	9	7/124 (5.65%)	8
Gastrointestinal disorders
Abdominal pain ^† 1	10/127 (7.87%)	11	16/124 (12.90%)	18
Abdominal pain upper ^† 1	12/127 (9.45%)	17	6/124 (4.84%)	6
Constipation ^† 1	18/127 (14.17%)	27	19/124 (15.32%)	25
Diarrhoea ^† 1	70/127 (55.12%)	213	45/124 (36.29%)	88
Dyspepsia ^† 1	8/127 (6.30%)	9	9/124 (7.26%)	11
Nausea ^† 1	47/127 (37.01%)	68	34/124 (27.42%)	56
Stomatitis ^† 1	17/127 (13.39%)	24	11/124 (8.87%)	22
Vomiting ^† 1	31/127 (24.41%)	42	21/124 (16.94%)	33
Haemorrhoids ^† 1	7/127 (5.51%)	7	2/124 (1.61%)	2
General disorders
Asthenia ^† 1	39/127 (30.71%)	76	32/124 (25.81%)	77
Chest Pain ^† 1	9/127 (7.09%)	11	9/124 (7.26%)	11
Chills ^† 1	8/127 (6.30%)	8	7/124 (5.65%)	8
Fatigue ^† 1	21/127 (16.54%)	33	25/124 (20.16%)	43
Influenza like illness ^† 1	10/127 (7.87%)	17	7/124 (5.65%)	10
Mucosal inflammation ^† 1	14/127 (11.02%)	20	13/124 (10.48%)	15
Oedema peripheral ^† 1	34/127 (26.77%)	53	23/124 (18.55%)	34
Pyrexia ^† 1	17/127 (13.39%)	22	13/124 (10.48%)	14
Infections and infestations
Influenza ^† 1	6/127 (4.72%)	10	7/124 (5.65%)	12
Nasopharyngitis ^† 1	13/127 (10.24%)	21	7/124 (5.65%)	8
Upper respiratory tract infection ^† 1	13/127 (10.24%)	36	15/124 (12.10%)	23
Urinary tract infection ^† 1	17/127 (13.39%)	25	16/124 (12.90%)	20
Paronychia ^† 1	7/127 (5.51%)	12	3/124 (2.42%)	6
Investigations
Ejection fraction decreased ^† 1	13/127 (10.24%)	19	8/124 (6.45%)	9
Weight decreased ^† 1	14/127 (11.02%)	16	11/124 (8.87%)	12
Weight increased ^† 1	11/127 (8.66%)	13	5/124 (4.03%)	10
Metabolism and nutrition disorders
Decreased appetite ^† 1	23/127 (18.11%)	27	10/124 (8.06%)	14
Hyperglycaemia ^† 1	8/127 (6.30%)	17	5/124 (4.03%)	9
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	38/127 (29.92%)	60	31/124 (25.00%)	49
Back pain ^† 1	23/127 (18.11%)	29	21/124 (16.94%)	27
Bone pain ^† 1	16/127 (12.60%)	25	10/124 (8.06%)	12
Muscle spasms ^† 1	14/127 (11.02%)	17	5/124 (4.03%)	6
Musculoskeletal chest pain ^† 1	11/127 (8.66%)	13	4/124 (3.23%)	6
Musculoskeletal pain ^† 1	11/127 (8.66%)	11	6/124 (4.84%)	8
Myalgia ^† 1	12/127 (9.45%)	16	9/124 (7.26%)	9
Pain in extremity ^† 1	22/127 (17.32%)	44	16/124 (12.90%)	23
Nervous system disorders
Dizziness ^† 1	21/127 (16.54%)	32	12/124 (9.68%)	12
Headache ^† 1	22/127 (17.32%)	33	14/124 (11.29%)	24
Neuropathy peripheral ^† 1	18/127 (14.17%)	26	17/124 (13.71%)	19
Paraesthesia ^† 1	13/127 (10.24%)	19	11/124 (8.87%)	13
Peripheral sensory neuropathy ^† 1	10/127 (7.87%)	12	9/124 (7.26%)	9
Psychiatric disorders
Anxiety ^† 1	14/127 (11.02%)	15	5/124 (4.03%)	6
Depression ^† 1	13/127 (10.24%)	14	5/124 (4.03%)	6
Insomnia ^† 1	15/127 (11.81%)	18	18/124 (14.52%)	23
Renal and urinary disorders
Dysuria ^† 1	9/127 (7.09%)	14	2/124 (1.61%)	4
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	25/127 (19.69%)	36	18/124 (14.52%)	27
Dyspnoea ^† 1	20/127 (15.75%)	22	13/124 (10.48%)	17
Epistaxis ^† 1	14/127 (11.02%)	18	13/124 (10.48%)	20
Skin and subcutaneous tissue disorders
Alopecia ^† 1	38/127 (29.92%)	40	40/124 (32.26%)	50
Dry skin ^† 1	8/127 (6.30%)	10	6/124 (4.84%)	7
Nail disorder ^† 1	9/127 (7.09%)	13	5/124 (4.03%)	7
Pruritus ^† 1	20/127 (15.75%)	42	14/124 (11.29%)	19
Rash ^† 1	23/127 (18.11%)	35	12/124 (9.68%)	17
Vascular disorders
Hot flush ^† 1	9/127 (7.09%)	14	9/124 (7.26%)	17
Hypertension ^† 1	22/127 (17.32%)	54	24/124 (19.35%)	65
Lymphoedema ^† 1	7/127 (5.51%)	10	5/124 (4.03%)	5
1 Term from vocabulary, MedDRA version 22.1 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Medical Communications
Organization:	Hoffmann-La Roche
Phone:	800 821-8590
EMail:	genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rimawi M, Ferrero JM, de la Haba-Rodriguez J, Poole C, De Placido S, Osborne CK, Hegg R, Easton V, Wohlfarth C, Arpino G; PERTAIN Study Group. First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab, in Human Epidermal Growth Factor Receptor 2-Positive and Hormone Receptor-Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A Randomized, Open-Label Phase II Trial. J Clin Oncol. 2018 Oct 1;36(28):2826-2835. doi: 10.1200/JCO.2017.76.7863. Epub 2018 Aug 14.

Layout table for additonal information

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01491737
Other Study ID Numbers:	MO27775 2011-002132-10 ( EudraCT Number )
First Submitted:	December 6, 2011
First Posted:	December 14, 2011
Results First Submitted:	May 11, 2017
Results First Posted:	June 7, 2017
Last Update Posted:	October 28, 2020

To Top