Trial Outcomes & Findings for A Study to Evaluate Patient Preference and Satisfaction of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Participants With HER2-Positive Early Breast Cancer (NCT NCT03674112)

NCT ID: NCT03674112

Last Updated: 2024-01-02

Results Overview

Question 1 of the Patient Preference Questionnaire (PPQ) asked participants the following question: "All things considered, which method of administration did you prefer?" The three available options for a participant's response were: IV, SC, or No preference. A point estimate with associated exact Clopper-Pearson binomial 95% confidence interval was calculated only for the percentage of participants who preferred PH FDC SC.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 160 participants
• Primary outcome timeframe: Cycle 6 Day 1 (each cycle is 21 days)
• Results posted on: 2024-01-02

Participant Flow

A total of 183 patients were screened and 160 participants were enrolled.

Participant milestones

Measure	A: P+H IV Followed by PH FDC SC In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.
Treatment Cross-Over (Cycles 1 to 6) STARTED	80	80
Treatment Cross-Over (Cycles 1 to 6) Completed Cross-Over Treatment	80	80
Treatment Cross-Over (Cycles 1 to 6) COMPLETED	79	80
Treatment Cross-Over (Cycles 1 to 6) NOT COMPLETED	1	0
Treatment Continuation (Cycles 7 to ≤18) STARTED	79	80
Treatment Continuation (Cycles 7 to ≤18) Received PH FDC SC for Treatment Continuation	70	68
Treatment Continuation (Cycles 7 to ≤18) Received P+H IV for Treatment Continuation	9	12
Treatment Continuation (Cycles 7 to ≤18) Completed Continuation Treatment	78	77
Treatment Continuation (Cycles 7 to ≤18) COMPLETED	78	77
Treatment Continuation (Cycles 7 to ≤18) NOT COMPLETED	1	3
Follow-Up Period (≥3 Years) STARTED	80	79
Follow-Up Period (≥3 Years) COMPLETED	73	75
Follow-Up Period (≥3 Years) NOT COMPLETED	7	4

Reasons for withdrawal

Measure	A: P+H IV Followed by PH FDC SC In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.
Treatment Cross-Over (Cycles 1 to 6) Adverse Event	1	0
Treatment Continuation (Cycles 7 to ≤18) Reason Not Specified	0	2
Treatment Continuation (Cycles 7 to ≤18) Withdrawal by Subject	0	1
Treatment Continuation (Cycles 7 to ≤18) Disease Relapse	1	0
Follow-Up Period (≥3 Years) Withdrawal by Subject	2	2
Follow-Up Period (≥3 Years) Lost to Follow-up	2	1
Follow-Up Period (≥3 Years) Death	2	0
Follow-Up Period (≥3 Years) Reason Not Specified	1	1

Baseline Characteristics

A Study to Evaluate Patient Preference and Satisfaction of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Participants With HER2-Positive Early Breast Cancer

Baseline characteristics by cohort

Measure	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Total n=160 Participants Total of all reporting groups
Age, Continuous	49.4 Years STANDARD_DEVIATION 11.6 • n=5 Participants	48.2 Years STANDARD_DEVIATION 12.1 • n=7 Participants	48.8 Years STANDARD_DEVIATION 11.8 • n=5 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	80 Participants n=7 Participants	160 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	21 Participants n=7 Participants	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	59 Participants n=5 Participants	54 Participants n=7 Participants	113 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	62 Participants n=5 Participants	67 Participants n=7 Participants	129 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Baseline Weight	67.36 kilograms (kg) STANDARD_DEVIATION 12.08 • n=5 Participants	70.21 kilograms (kg) STANDARD_DEVIATION 14.15 • n=7 Participants	68.78 kilograms (kg) STANDARD_DEVIATION 13.20 • n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline ECOG Peformance Status 0	70 Participants n=5 Participants	70 Participants n=7 Participants	140 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline ECOG Peformance Status 1	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Number of Cycles of Prior Neoadjuvant Pertuzumab IV and Trastuzumab IV <4 Cycles	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Number of Cycles of Prior Neoadjuvant Pertuzumab IV and Trastuzumab IV ≥4 Cycles	75 Participants n=5 Participants	70 Participants n=7 Participants	145 Participants n=5 Participants
Prior Neoadjuvant Chemotherapy Regimen Anthracyclines + Taxanes	55 Participants n=5 Participants	53 Participants n=7 Participants	108 Participants n=5 Participants
Prior Neoadjuvant Chemotherapy Regimen Carboplatin + Taxanes	22 Participants n=5 Participants	23 Participants n=7 Participants	45 Participants n=5 Participants
Prior Neoadjuvant Chemotherapy Regimen Taxanes Only	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Pathological Complete Response (pCR) to Prior Neoadjuvant Treatment pCR	52 Participants n=5 Participants	50 Participants n=7 Participants	102 Participants n=5 Participants
Pathological Complete Response (pCR) to Prior Neoadjuvant Treatment Non-pCR	28 Participants n=5 Participants	30 Participants n=7 Participants	58 Participants n=5 Participants
Hormone Receptor Status Estrogen Receptor (ER)-Positive and/or Progesterone Receptor (PgR)-Positive	53 Participants n=5 Participants	51 Participants n=7 Participants	104 Participants n=5 Participants
Hormone Receptor Status ER-Negative and PgR-Negative	27 Participants n=5 Participants	29 Participants n=7 Participants	56 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 6 Day 1 (each cycle is 21 days)

Population: Modified Intent-to-Treat (mITT) Population: All randomized participants, allocated to their randomized treatment arm, who received at least one dose by both SC and IV routes of administration during the Treatment Cross-over Period and subsequently answered at least Question 1 of the PPQ.

Question 1 of the Patient Preference Questionnaire (PPQ) asked participants the following question: "All things considered, which method of administration did you prefer?" The three available options for a participant's response were: IV, SC, or No preference. A point estimate with associated exact Clopper-Pearson binomial 95% confidence interval was calculated only for the percentage of participants who preferred PH FDC SC.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Percentage of Participants by Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 1 of the Patient Preference Questionnaire (PPQ) SC Preference	85.00 Percentage of participants Interval 78.51 to 90.15	87.50 Percentage of participants Interval 78.21 to 93.84	82.50 Percentage of participants Interval 72.38 to 90.09	—	—	—
Percentage of Participants by Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 1 of the Patient Preference Questionnaire (PPQ) IV Preference	13.8 Percentage of participants As per the statistical analysis plan, a 95% confidence interval was only calculated for the percentage of participants who preferred PH FDC SC.	12.5 Percentage of participants As per the statistical analysis plan, a 95% confidence interval was only calculated for the percentage of participants who preferred PH FDC SC.	15.0 Percentage of participants As per the statistical analysis plan, a 95% confidence interval was only calculated for the percentage of participants who preferred PH FDC SC.	—	—	—
Percentage of Participants by Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 1 of the Patient Preference Questionnaire (PPQ) No Preference	1.3 Percentage of participants As per the statistical analysis plan, a 95% confidence interval was only calculated for the percentage of participants who preferred PH FDC SC.	0.0 Percentage of participants As per the statistical analysis plan, a 95% confidence interval was only calculated for the percentage of participants who preferred PH FDC SC.	2.5 Percentage of participants As per the statistical analysis plan, a 95% confidence interval was only calculated for the percentage of participants who preferred PH FDC SC.	—	—	—

SECONDARY outcome

Timeframe: Cycle 6 Day 1 (each cycle is 21 days)

Population: Modified ITT (mITT) Population; for Question 2 of the PPQ, the number analyzed for the strength of SC or IV preference represents the participants who indicated in their responses to Question 1 of the PPQ that they preferred the SC or IV route of administration, respectively.

Question 1 of the Patient Preference Questionnaire (PPQ) was as follows: "All things considered, which method of administration did you prefer?" The available options for a participant's response were IV, SC, or No preference. In Question 2 of the PPQ, participants who reported a preference for one of the two administration routes in Question 1 of the PPQ were asked to rate the strength of their preference (very strong, fairly strong, not very strong).

Outcome measures

Measure	All Participants n=158 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=78 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Percentage of Participants by Responses to the Strength of Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 2 of the Patient Preference Questionnaire (PPQ) SC Preference: Very Strong	67.6 Percentage of participants	68.6 Percentage of participants	66.7 Percentage of participants	—	—	—
Percentage of Participants by Responses to the Strength of Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 2 of the Patient Preference Questionnaire (PPQ) SC Preference: Fairly Strong	25.0 Percentage of participants	24.3 Percentage of participants	25.8 Percentage of participants	—	—	—
Percentage of Participants by Responses to the Strength of Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 2 of the Patient Preference Questionnaire (PPQ) SC Preference: Not Very Strong	7.4 Percentage of participants	7.1 Percentage of participants	7.6 Percentage of participants	—	—	—
Percentage of Participants by Responses to the Strength of Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 2 of the Patient Preference Questionnaire (PPQ) IV Preference: Very Strong	54.5 Percentage of participants	40.0 Percentage of participants	66.7 Percentage of participants	—	—	—
Percentage of Participants by Responses to the Strength of Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 2 of the Patient Preference Questionnaire (PPQ) IV Preference: Fairly Strong	9.1 Percentage of participants	10.0 Percentage of participants	8.3 Percentage of participants	—	—	—
Percentage of Participants by Responses to the Strength of Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 2 of the Patient Preference Questionnaire (PPQ) IV Preference: Not Very Strong	36.4 Percentage of participants	50.0 Percentage of participants	25.0 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Cycle 6 Day 1 (each cycle is 21 days)

Population: Modified ITT (mITT) Population; for Question 3, the number analyzed for the two main reasons for SC or IV preference represents the participants who indicated in their responses to Question 1 of the PPQ that they preferred the SC or IV route of administration, respectively.

In Question 3 of the PPQ, participants who reported a preference for one of the two administration routes in Question 1 of the PPQ were asked to provide the two main reasons for their preference. The five available options for a participant's response were: Feels less emotionally distressing; Requires less time in the clinic; Lower level of injection-site pain; Feels more comfortable during administration; and Other reason.

Outcome measures

Measure	All Participants n=324 Responses In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=160 Responses In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=164 Responses In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ) SC Preference: Feels Less Emotionally Distressing	16.3 Percentage of responses	14.7 Percentage of responses	18.0 Percentage of responses	—	—	—
Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ) SC Preference: Requires Less Time in the Clinic	42.2 Percentage of responses	42.0 Percentage of responses	42.4 Percentage of responses	—	—	—
Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ) SC Preference: Lower Level of Injection-Site Pain	11.3 Percentage of responses	9.8 Percentage of responses	12.9 Percentage of responses	—	—	—
Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ) SC Preference: Feels More Comfortable During Administration	25.9 Percentage of responses	28.7 Percentage of responses	23.0 Percentage of responses	—	—	—
Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ) SC Preference: Other Reason	4.3 Percentage of responses	4.9 Percentage of responses	3.6 Percentage of responses	—	—	—
Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ) IV Preference: Feels Less Emotionally Distressing	16.7 Percentage of responses	17.6 Percentage of responses	16.0 Percentage of responses	—	—	—
Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ) IV Preference: Requires Less Time in the Clinic	4.8 Percentage of responses	5.9 Percentage of responses	4.0 Percentage of responses	—	—	—
Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ) IV Preference: Lower Level of Injection-Site Pain	26.2 Percentage of responses	23.5 Percentage of responses	28.0 Percentage of responses	—	—	—
Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ) IV Preference: Feels More Comfortable During Administration	33.3 Percentage of responses	47.1 Percentage of responses	24.0 Percentage of responses	—	—	—
Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ) IV Preference: Other Reason	19.0 Percentage of responses	5.9 Percentage of responses	28.0 Percentage of responses	—	—	—

SECONDARY outcome

Timeframe: Cycle 3 Day 1, Cycle 6 Day 1 (each cycle is 21 days)

Population: Modified Intent-to-Treat (mITT) Population

The Therapy Administration Satisfaction Questionnaire (TASQ) is a 12-item, patient-reported questionnaire measuring the impact of each mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on five domains: Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. The TASQ-IV/-SC was administered at treatment Cycles 3 and 6 according to the order of treatment received per arm during the Cross-Over Period. Question 1 of the TASQ-IV/TASQ-SC is one of two items in the Satisfaction domain, with participants providing their answers to the following question: "How satisfied or dissatisfied were you with the IV infusion/SC injection?" The five available options for a participant's response were: very satisfied, satisfied, neither satisfied nor dissatisfied, dissatisfied, and very dissatisfied.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=160 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Percentage of Participants by Their Level of Satisfaction With the Respective Methods of Administration (IV and SC), Question 1 of the Therapy Administration Satisfaction Questionnaire -Intravenous (TASQ-IV) and -Subcutaneous (TASQ-SC) Very Satisfied	25.6 Percentage of participants	57.5 Percentage of participants	—	—	—	—
Percentage of Participants by Their Level of Satisfaction With the Respective Methods of Administration (IV and SC), Question 1 of the Therapy Administration Satisfaction Questionnaire -Intravenous (TASQ-IV) and -Subcutaneous (TASQ-SC) Satisfied	41.9 Percentage of participants	30.6 Percentage of participants	—	—	—	—
Percentage of Participants by Their Level of Satisfaction With the Respective Methods of Administration (IV and SC), Question 1 of the Therapy Administration Satisfaction Questionnaire -Intravenous (TASQ-IV) and -Subcutaneous (TASQ-SC) Neither Satisfied nor Dissatisfied	25.6 Percentage of participants	4.4 Percentage of participants	—	—	—	—
Percentage of Participants by Their Level of Satisfaction With the Respective Methods of Administration (IV and SC), Question 1 of the Therapy Administration Satisfaction Questionnaire -Intravenous (TASQ-IV) and -Subcutaneous (TASQ-SC) Dissatisfied	5.6 Percentage of participants	1.9 Percentage of participants	—	—	—	—
Percentage of Participants by Their Level of Satisfaction With the Respective Methods of Administration (IV and SC), Question 1 of the Therapy Administration Satisfaction Questionnaire -Intravenous (TASQ-IV) and -Subcutaneous (TASQ-SC) Very Dissatisfied	1.3 Percentage of participants	4.4 Percentage of participants	—	—	—	—
Percentage of Participants by Their Level of Satisfaction With the Respective Methods of Administration (IV and SC), Question 1 of the Therapy Administration Satisfaction Questionnaire -Intravenous (TASQ-IV) and -Subcutaneous (TASQ-SC) Did Not Answer Question	0.0 Percentage of participants	1.3 Percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 3 Day 1, Cycle 6 Day 1 (each cycle is 21 days)

Population: Modified Intent-to-Treat (mITT) Population; The number analyzed indicates the number of participants who completed the TASQ-IV/-SC questionnaire items within a domain.

The TASQ is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains: Physical Impact (3 items: Question [Q]2. Pain, Q3. Swelling, Q4. Redness), Psychological Impact (1 item: Q5. Feeling restricted), Impact on Activities of Daily Living (1 item: Q8. Lost/gained time), Convenience (2 items: Q6. Is it convenient?, Q7. Bothered by the amount of time?), and Satisfaction (2 items: Q1. How satisfied or dissatisfied are you with treatment?, Q12: Would you recommend the way you received the treatment?). In addition, 3 questions in the TASQ (Q9, Q10, Q11) are not part of the domains. Responses for the 3 domains that contain more than 1 item were scored from 0 to 100, with a higher score indicating a better outcome. Responses for the 2 domains with 1 item were scored from 1 to 5, with a higher score indicating a better outcome.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=160 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Mean Scores of the Five Domains of the TASQ-IV and TASQ-SC (Satisfaction, Physical Impact, Psychological Impact, Impact on Activities of Daily Living, and Convenience) to Assess the Impact of IV and SC Routes of Administration Satisfaction Domain	64.3 Score on a scale Standard Deviation 23.6	87.7 Score on a scale Standard Deviation 17.5	—	—	—	—
Mean Scores of the Five Domains of the TASQ-IV and TASQ-SC (Satisfaction, Physical Impact, Psychological Impact, Impact on Activities of Daily Living, and Convenience) to Assess the Impact of IV and SC Routes of Administration Physical Impact Domain	86.5 Score on a scale Standard Deviation 14.8	81.3 Score on a scale Standard Deviation 15.4	—	—	—	—
Mean Scores of the Five Domains of the TASQ-IV and TASQ-SC (Satisfaction, Physical Impact, Psychological Impact, Impact on Activities of Daily Living, and Convenience) to Assess the Impact of IV and SC Routes of Administration Psychological Impact Domain	3.8 Score on a scale Standard Deviation 1.2	4.6 Score on a scale Standard Deviation 0.7	—	—	—	—
Mean Scores of the Five Domains of the TASQ-IV and TASQ-SC (Satisfaction, Physical Impact, Psychological Impact, Impact on Activities of Daily Living, and Convenience) to Assess the Impact of IV and SC Routes of Administration Impact on Activities of Daily Living Domain	2.3 Score on a scale Standard Deviation 0.9	3.9 Score on a scale Standard Deviation 1.0	—	—	—	—
Mean Scores of the Five Domains of the TASQ-IV and TASQ-SC (Satisfaction, Physical Impact, Psychological Impact, Impact on Activities of Daily Living, and Convenience) to Assess the Impact of IV and SC Routes of Administration Convenience Domain	56.8 Score on a scale Standard Deviation 26.0	90.0 Score on a scale Standard Deviation 13.8	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 3 Day 1 and Cycle 6 Day 1 (each cycle is 21 days)

Population: Modified Intent-to-Treat (mITT) Population

The TASQ is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains. In addition, 3 questions (Q.9-11) are not part of the domains. The TASQ-IV/-SC was administered at treatment Cycles 3 and 6 according to the order of treatment received per arm during the Cross-Over Period. Question 9 asked the participant, "When you receive the IV infusion/SC injection treatment, are you able to talk to your nurse and/or doctor as much as you would like about your illness?" There were five available response options: a) Yes, I had more than enough time to talk to my nurse and/or doctor; b) Yes, but I would have liked more time to talk to my nurse and/or doctor; c) It does not matter to me if I have time to talk to my nurse and/or doctor during my treatment; d) No, I did not have enough time to talk to my nurse and/or doctor; and e) No, I did not talk to my nurse and/or doctor at all.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=160 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Percentage of Participants by Their Responses to Question 9 of the TASQ-IV and TASQ-SC, Assessing Whether Participants Receiving IV and SC Administration Have as Much Time as They Would Like to Talk to Their Nurse and/or Doctor About Their Illness a) Yes, I had enough time to talk to my nurse and/or doctor	82.5 Percentage of participants	90.0 Percentage of participants	—	—	—	—
Percentage of Participants by Their Responses to Question 9 of the TASQ-IV and TASQ-SC, Assessing Whether Participants Receiving IV and SC Administration Have as Much Time as They Would Like to Talk to Their Nurse and/or Doctor About Their Illness b) Yes, but I would have liked more time to talk to my nurse and/or doctor	9.4 Percentage of participants	5.0 Percentage of participants	—	—	—	—
Percentage of Participants by Their Responses to Question 9 of the TASQ-IV and TASQ-SC, Assessing Whether Participants Receiving IV and SC Administration Have as Much Time as They Would Like to Talk to Their Nurse and/or Doctor About Their Illness c) It does not matter to me if I have time to talk to my nurse and/or doctor	5.0 Percentage of participants	3.1 Percentage of participants	—	—	—	—
Percentage of Participants by Their Responses to Question 9 of the TASQ-IV and TASQ-SC, Assessing Whether Participants Receiving IV and SC Administration Have as Much Time as They Would Like to Talk to Their Nurse and/or Doctor About Their Illness d) No, I did not have enough time to talk to my nurse and/or doctor	0.6 Percentage of participants	0.6 Percentage of participants	—	—	—	—
Percentage of Participants by Their Responses to Question 9 of the TASQ-IV and TASQ-SC, Assessing Whether Participants Receiving IV and SC Administration Have as Much Time as They Would Like to Talk to Their Nurse and/or Doctor About Their Illness e) No, I did not talk to my nurse and/or doctor at all	2.5 Percentage of participants	0.0 Percentage of participants	—	—	—	—
Percentage of Participants by Their Responses to Question 9 of the TASQ-IV and TASQ-SC, Assessing Whether Participants Receiving IV and SC Administration Have as Much Time as They Would Like to Talk to Their Nurse and/or Doctor About Their Illness Patient did not answer question	0.0 Percentage of participants	1.3 Percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 3 Day 1 and Cycle 6 Day 1 (each cycle is 21 days)

Population: Modified Intent-to-Treat (mITT) Population

The Therapy Administration Satisfaction Questionnaire (TASQ) is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains (questions [Q] 1 to 8 and Q12): Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. In addition, 3 questions in the TASQ-IV/-SC (Q 9-11) are not part of the domains. The TASQ-IV/-SC were administered at treatment Cycles 3 and 6 according to the order of treatment received in each study arm during the Cross-Over Period. Question 10 of the TASQ-IV/-SC asked the participant "Does the IV infusion/SC injection impact the amount of time you have to talk to your nurse and/or doctor about your illness and other concerns?" There were two available options for the participant's response: Yes or No.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=160 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Percentage of Participants by Their Responses to Question 10 of the TASQ-IV and TASQ-SC, Assessing Whether IV and SC Administration Have an Impact on the Amount of Time Participants Have to Talk to Their Nurse and/or Doctor About Their Illness Yes	20.0 Percentage of participants	13.1 Percentage of participants	—	—	—	—
Percentage of Participants by Their Responses to Question 10 of the TASQ-IV and TASQ-SC, Assessing Whether IV and SC Administration Have an Impact on the Amount of Time Participants Have to Talk to Their Nurse and/or Doctor About Their Illness No	79.4 Percentage of participants	85.0 Percentage of participants	—	—	—	—
Percentage of Participants by Their Responses to Question 10 of the TASQ-IV and TASQ-SC, Assessing Whether IV and SC Administration Have an Impact on the Amount of Time Participants Have to Talk to Their Nurse and/or Doctor About Their Illness Patient Did Not Answer Question	0.6 Percentage of participants	1.9 Percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 3 Day 1 and Cycle 6 Day 1 (each cycle is 21 days)

Population: Modified Intent-to-Treat (mITT) Population

The Therapy Administration Satisfaction Questionnaire (TASQ) is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains (questions [Q] 1 to 8 and Q12): Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. In addition, 3 questions in the TASQ-IV/-SC (Q 9-11) are not part of the domains. The TASQ-IV/-SC was administered at treatment Cycles 3 and 6 according to the order of treatment received during the Cross-Over Period. Question 11 of the TASQ-IV/-SC asked the participant, "There are two ways to get cancer treatment: a) IV infusion given through a port or small tube; b) SC (subcutaneous) injection in your thigh. Which would you prefer?" There were three available options for the participant's response: IV, SC, or No Preference.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=160 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Percentage of Participants by Their Responses to Question 11 of the TASQ-IV and TASQ-SC, Assessing the Participants' Preferred Method for Receiving Cancer Treatment Prefer IV Method	11.9 Percentage of participants	9.4 Percentage of participants	—	—	—	—
Percentage of Participants by Their Responses to Question 11 of the TASQ-IV and TASQ-SC, Assessing the Participants' Preferred Method for Receiving Cancer Treatment Prefer SC Method	70.6 Percentage of participants	82.5 Percentage of participants	—	—	—	—
Percentage of Participants by Their Responses to Question 11 of the TASQ-IV and TASQ-SC, Assessing the Participants' Preferred Method for Receiving Cancer Treatment No Preference	11.9 Percentage of participants	5.6 Percentage of participants	—	—	—	—
Percentage of Participants by Their Responses to Question 11 of the TASQ-IV and TASQ-SC, Assessing the Participants' Preferred Method for Receiving Cancer Treatment Patient Did Not Answer Question	5.6 Percentage of participants	2.5 Percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 6 Day 1 (each cycle is 21 days)

Population: All randomized participants, allocated to their randomized treatment arm.

At treatment Cycle 6, Day 1, participants were expected to select the study treatment formulation (PH FDC SC or P+H IV) they would receive during the Treatment Continuation Period (starting at Cycle 7) to complete their 18 cycles of neo/adjuvant HER2-targeted treatment. Additionally, for each participant's preference category (SC, IV, and No preference) as per the question 1 of the patient preference questionnaire (PPQ), the percentage of participants who selected each treatment administration route for the Treatment Continuation Period (PH FDC SC or P+H IV) was summarized.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Percentage of Participants by Their Choice of Treatment in the Treatment Continuation Period (PH FDC SC or P+H IV) and by Consistency of This Choice With Their Preferred Method of Administration Reported in Question 1 of the PPQ Chose PH FDC SC for Treatment Continuation	86.9 Percentage of participants	88.8 Percentage of participants	85.0 Percentage of participants	—	—	—
Percentage of Participants by Their Choice of Treatment in the Treatment Continuation Period (PH FDC SC or P+H IV) and by Consistency of This Choice With Their Preferred Method of Administration Reported in Question 1 of the PPQ Chose P+H IV for Treatment Continuation	13.1 Percentage of participants	11.3 Percentage of participants	15.0 Percentage of participants	—	—	—
Percentage of Participants by Their Choice of Treatment in the Treatment Continuation Period (PH FDC SC or P+H IV) and by Consistency of This Choice With Their Preferred Method of Administration Reported in Question 1 of the PPQ Preferred SC per the PPQ and Chose PH FDC SC for Continuation	85.0 Percentage of participants	87.5 Percentage of participants	82.5 Percentage of participants	—	—	—
Percentage of Participants by Their Choice of Treatment in the Treatment Continuation Period (PH FDC SC or P+H IV) and by Consistency of This Choice With Their Preferred Method of Administration Reported in Question 1 of the PPQ Preferred SC per the PPQ and Chose P+H IV for Continuation	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	—	—	—
Percentage of Participants by Their Choice of Treatment in the Treatment Continuation Period (PH FDC SC or P+H IV) and by Consistency of This Choice With Their Preferred Method of Administration Reported in Question 1 of the PPQ Preferred IV per the PPQ and Chose PH FDC SC for Continuation	0.6 Percentage of participants	1.3 Percentage of participants	0.0 Percentage of participants	—	—	—
Percentage of Participants by Their Choice of Treatment in the Treatment Continuation Period (PH FDC SC or P+H IV) and by Consistency of This Choice With Their Preferred Method of Administration Reported in Question 1 of the PPQ Preferred IV per the PPQ and Chose P+H IV for Continuation	13.1 Percentage of participants	11.3 Percentage of participants	15.0 Percentage of participants	—	—	—
Percentage of Participants by Their Choice of Treatment in the Treatment Continuation Period (PH FDC SC or P+H IV) and by Consistency of This Choice With Their Preferred Method of Administration Reported in Question 1 of the PPQ No Preference per the PPQ and Chose PH FDC SC for Continuation	1.3 Percentage of participants	0.0 Percentage of participants	2.5 Percentage of participants	—	—	—
Percentage of Participants by Their Choice of Treatment in the Treatment Continuation Period (PH FDC SC or P+H IV) and by Consistency of This Choice With Their Preferred Method of Administration Reported in Question 1 of the PPQ No Preference per the PPQ and Chose P+H IV for Continuation	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycles 1-6 (each cycle is 21 days)

Population: The number analyzed includes HCPs who completed question 1 of the survey per treatment cycle. For the questions related to IV access, the number analyzed only includes HCP responses for participants who required new IV access at a given treatment cycle.

The Healthcare Professional Questionnaire (HCPQ)-Treatment Room Question 1 was completed at each treatment cycle of the Treatment Cross-Over Period by the healthcare professionals (HCPs) who administered treatment to the study's participants. HCPs responded to the following parts of Question 1 that sought to evaluate the amount of time it took to complete activities related to treatment administration: "If new IV access was needed for this cycle of treatment, please indicate what type of IV access was provided (central venous catheter, peripherally inserted central catheter, or peripheral vein cannulation) and how long (in minutes) this took to set up (only for participants receiving IV treatment)? How long (in minutes) did it take to administer the treatment, i.e. total infusion duration? How long (in minutes) was the patient in the Treatment Room for in total?"

Outcome measures

Measure	All Participants n=80 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 1. Duration of Central Venous Catheter Set Up (IV Only)?	5.0 minutes Interval 4.0 to 6.0	—	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 1. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)?	5.0 minutes Interval 5.0 to 5.0	—	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 1. Duration of Peripheral Vein Cannulation Set Up (IV Only)?	5.0 minutes Interval 1.0 to 40.0	—	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 1. How Long Did it Take to Administer the Treatment?	150.0 minutes Interval 60.0 to 396.0	8.0 minutes Interval 2.0 to 17.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 1. How Long Was the Patient in the Treatment Room in Total?	300.0 minutes Interval 90.0 to 450.0	50.0 minutes Interval 8.0 to 240.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 2. Duration of Central Venous Catheter Set Up (IV Only)?	5.0 minutes Interval 3.0 to 5.0	—	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 2. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)?	3.0 minutes Interval 3.0 to 3.0	—	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 2. Duration of Peripheral Vein Cannulation Set Up (IV Only)?	5.0 minutes Interval 1.0 to 20.0	—	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 2. How Long Did it Take to Administer the Treatment?	90.0 minutes Interval 8.0 to 260.0	8.0 minutes Interval 5.0 to 20.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 2. How Long Was the Patient in the Treatment Room in Total?	153.0 minutes Interval 30.0 to 342.0	40.0 minutes Interval 8.0 to 225.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 3. Duration of Central Venous Catheter Set Up (IV Only)?	5.0 minutes Interval 3.0 to 10.0	—	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 3. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)?	3.0 minutes Interval 3.0 to 3.0	—	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 3. Duration of Peripheral Vein Cannulation Set Up (IV Only)?	5.0 minutes Interval 1.0 to 30.0	—	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 3. How Long Did it Take to Administer the Treatment?	70.0 minutes Interval 30.0 to 240.0	7.5 minutes Interval 4.0 to 16.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 3. How Long Was the Patient in the Treatment Room in Total?	150.0 minutes Interval 105.0 to 330.0	36.0 minutes Interval 5.0 to 327.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 4. Duration of Central Venous Catheter Set Up (IV Only)?	—	5.0 minutes Interval 2.0 to 10.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 4. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)?	—	42.0 minutes Interval 42.0 to 42.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 4. Duration of Peripheral Vein Cannulation Set Up (IV Only)?	—	5.0 minutes Interval 1.0 to 20.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 4. How Long Did it Take to Administer the Treatment?	8.0 minutes Interval 4.0 to 12.0	60.0 minutes Interval 30.0 to 210.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 4. How Long Was the Patient in the Treatment Room in Total?	45.0 minutes Interval 1.0 to 185.0	150.0 minutes Interval 80.0 to 480.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 5. Duration of Central Venous Catheter Set Up (IV Only)?	—	3.0 minutes Interval 2.0 to 10.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 5. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)?	—	10.0 minutes Interval 10.0 to 10.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 5. Duration of Peripheral Vein Cannulation Set Up (IV Only)?	—	5.0 minutes Interval 1.0 to 20.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 5. How Long Did it Take to Administer the Treatment?	8.0 minutes Interval 3.0 to 14.0	83.0 minutes Interval 30.0 to 200.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 5. How Long Was the Patient in the Treatment Room in Total?	33.0 minutes Interval 8.0 to 135.0	150.0 minutes Interval 95.0 to 343.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 6. Duration of Central Venous Catheter Set Up (IV Only)?	—	10.0 minutes Interval 1.0 to 91.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 6. Duration of Peripheral Vein Cannulation Set Up (IV Only)?	—	5.0 minutes Interval 1.0 to 60.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 6. How Long Did it Take to Administer the Treatment?	7.0 minutes Interval 3.0 to 11.0	60.0 minutes Interval 5.0 to 275.0	—	—	—	—
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room Cycle 6. How Long Was the Patient in the Treatment Room in Total?	35.0 minutes Interval 10.0 to 150.0	130.0 minutes Interval 45.0 to 330.0	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 6 (each cycle is 21 days)

Population: The number analyzed includes healthcare professionals (HCPs) who completed any part of the survey at treatment Cycle 6.

HCPs who administered study treatment responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Treatment Room Question 2: "If all P+H IV infusions are switched to FDC SC injections, please indicate how strongly you agree or disagree with each of the following statements: a) Patients will be moved outside of infusion unit to receive FDC SC; b) FDC SC route will allow more flexible scheduling; c) More patients will be treated in the infusion unit; d) Waiting list for any P+H IV treatment at the infusion unit will be reduced; e) Staff resources will be redistributed to other departments of the hospital; f) There will still be sufficient interaction time between HCPs and patients; g) Staff will spend more time for further education/development; h) Staff will dedicate more time attending to administrative tasks for Perjeta-Herceptin patients; i) Patients will spend less time in the care unit; j) Administration by FDC SC injection is preferred by patients."

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement b): Answer Missing	5.7 Percentage of HCPs	3.8 Percentage of HCPs	7.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement b): Not Applicable	0.0 Percentage of HCPs	0.0 Percentage of HCPs	0.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement c): Strongly Disagree	2.5 Percentage of HCPs	1.3 Percentage of HCPs	3.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement c): Disagree	7.5 Percentage of HCPs	7.6 Percentage of HCPs	7.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement c): Neutral	15.1 Percentage of HCPs	17.7 Percentage of HCPs	12.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement c): Agree	30.2 Percentage of HCPs	29.1 Percentage of HCPs	31.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement c): Strongly Agree	37.1 Percentage of HCPs	36.7 Percentage of HCPs	37.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement c): Not Applicable	1.9 Percentage of HCPs	3.8 Percentage of HCPs	0.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement c): Answer Missing	5.7 Percentage of HCPs	3.8 Percentage of HCPs	7.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement d): Strongly Disagree	4.4 Percentage of HCPs	1.3 Percentage of HCPs	7.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement d): Disagree	8.2 Percentage of HCPs	8.9 Percentage of HCPs	7.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement d): Neutral	14.5 Percentage of HCPs	17.7 Percentage of HCPs	11.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement d): Agree	27.7 Percentage of HCPs	29.1 Percentage of HCPs	26.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement d): Strongly Agree	35.2 Percentage of HCPs	36.7 Percentage of HCPs	33.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement d): Not Applicable	3.8 Percentage of HCPs	2.5 Percentage of HCPs	5.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement d): Answer Missing	6.3 Percentage of HCPs	3.8 Percentage of HCPs	8.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement e): Strongly Disagree	12.6 Percentage of HCPs	15.2 Percentage of HCPs	10.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement e): Disagree	19.5 Percentage of HCPs	16.5 Percentage of HCPs	22.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement e): Neutral	20.1 Percentage of HCPs	17.7 Percentage of HCPs	22.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement e): Agree	15.1 Percentage of HCPs	19.0 Percentage of HCPs	11.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement e): Strongly Agree	19.5 Percentage of HCPs	20.3 Percentage of HCPs	18.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement e): Not Applicable	6.9 Percentage of HCPs	7.6 Percentage of HCPs	6.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement e): Answer Missing	6.3 Percentage of HCPs	3.8 Percentage of HCPs	8.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement f): Strongly Disagree	1.9 Percentage of HCPs	0.0 Percentage of HCPs	3.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement f): Disagree	5.0 Percentage of HCPs	6.3 Percentage of HCPs	3.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement f): Neutral	15.7 Percentage of HCPs	15.2 Percentage of HCPs	16.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement f): Agree	32.1 Percentage of HCPs	31.6 Percentage of HCPs	32.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement f): Strongly Agree	39.0 Percentage of HCPs	43.0 Percentage of HCPs	35.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement f): Not Applicable	0.0 Percentage of HCPs	0.0 Percentage of HCPs	0.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement f): Answer Missing	6.3 Percentage of HCPs	3.8 Percentage of HCPs	8.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement g): Strongly Disagree	2.5 Percentage of HCPs	0.0 Percentage of HCPs	5.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement g): Disagree	9.4 Percentage of HCPs	7.6 Percentage of HCPs	11.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement g): Neutral	27.7 Percentage of HCPs	31.6 Percentage of HCPs	23.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement g): Agree	21.4 Percentage of HCPs	20.3 Percentage of HCPs	22.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement g): Strongly Agree	31.4 Percentage of HCPs	35.4 Percentage of HCPs	27.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement g): Not Applicable	1.9 Percentage of HCPs	1.3 Percentage of HCPs	2.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement g): Answer Missing	5.7 Percentage of HCPs	3.8 Percentage of HCPs	7.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement h): Strongly Disagree	3.1 Percentage of HCPs	1.3 Percentage of HCPs	5.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement h): Disagree	13.8 Percentage of HCPs	11.4 Percentage of HCPs	16.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement h): Neutral	24.5 Percentage of HCPs	25.3 Percentage of HCPs	23.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement h): Agree	20.1 Percentage of HCPs	24.1 Percentage of HCPs	16.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement h): Strongly Agree	30.2 Percentage of HCPs	32.9 Percentage of HCPs	27.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement h): Not Applicable	2.5 Percentage of HCPs	1.3 Percentage of HCPs	3.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement h): Answer Missing	5.7 Percentage of HCPs	3.8 Percentage of HCPs	7.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement i): Strongly Disagree	0.0 Percentage of HCPs	0.0 Percentage of HCPs	0.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement i): Disagree	5.0 Percentage of HCPs	6.3 Percentage of HCPs	3.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement i): Neutral	3.1 Percentage of HCPs	1.3 Percentage of HCPs	5.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement i): Agree	25.2 Percentage of HCPs	27.8 Percentage of HCPs	22.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement i): Strongly Agree	60.4 Percentage of HCPs	60.8 Percentage of HCPs	60.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement i): Not Applicable	0.0 Percentage of HCPs	0.0 Percentage of HCPs	0.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement i): Answer Missing	6.3 Percentage of HCPs	3.8 Percentage of HCPs	8.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement j): Strongly Disagree	0.0 Percentage of HCPs	0.0 Percentage of HCPs	0.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement j): Disagree	5.0 Percentage of HCPs	8.9 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement j): Neutral	12.6 Percentage of HCPs	10.1 Percentage of HCPs	15.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement j): Agree	24.5 Percentage of HCPs	22.8 Percentage of HCPs	26.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement j): Strongly Agree	50.3 Percentage of HCPs	53.2 Percentage of HCPs	47.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement j): Not Applicable	1.3 Percentage of HCPs	1.3 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement j): Answer Missing	6.3 Percentage of HCPs	3.8 Percentage of HCPs	8.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement a): Strongly Disagree	16.4 Percentage of HCPs	11.4 Percentage of HCPs	21.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement a): Disagree	15.1 Percentage of HCPs	12.7 Percentage of HCPs	17.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement a): Neutral	6.3 Percentage of HCPs	8.9 Percentage of HCPs	3.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement a): Agree	21.4 Percentage of HCPs	26.6 Percentage of HCPs	16.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement a): Strongly Agree	22.6 Percentage of HCPs	22.8 Percentage of HCPs	22.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement a): Not Applicable	12.6 Percentage of HCPs	13.9 Percentage of HCPs	11.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement a): Answer Missing	5.7 Percentage of HCPs	3.8 Percentage of HCPs	7.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement b): Strongly Disagree	3.1 Percentage of HCPs	0.0 Percentage of HCPs	6.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement b): Disagree	8.8 Percentage of HCPs	7.6 Percentage of HCPs	10.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement b): Neutral	8.8 Percentage of HCPs	10.1 Percentage of HCPs	7.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement b): Agree	28.3 Percentage of HCPs	29.1 Percentage of HCPs	27.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room Statement b): Strongly Agree	45.3 Percentage of HCPs	49.4 Percentage of HCPs	41.3 Percentage of HCPs	—	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 6 (each cycle is 21 days)

Population: The number analyzed includes HCPs who completed any part of the survey at treatment Cycle 6.

Healthcare professionals (HCPs) who administered study treatment responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Treatment Room Questions 3 to 7: "Looking back over the Perjeta-Herceptin treatment sessions, please indicate based on your opinion which administration method: Q3. Which Method Was Most Convenient for the Patient? Q4. Which Method Was Best for Optimizing Patient Care in Your Centre? Q5. Which Method Took the Least Time from Start to Finish of Administration? Q6. Which Method Required the Least Resource Use for Administration? Q7. Which Method Was Preferred by Patients?" The four available response options were: P+H IV, FDC SC, No Difference, and Unsure.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q3. Answer: FDC SC	86.8 Percentage of HCPs	88.6 Percentage of HCPs	85.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q3. Answer: P+H IV	3.8 Percentage of HCPs	6.3 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q3. Answer: No Difference	3.8 Percentage of HCPs	2.5 Percentage of HCPs	5.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q3. Answer: Unsure	3.8 Percentage of HCPs	0.0 Percentage of HCPs	7.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q3. Answer: Missing	1.9 Percentage of HCPs	2.5 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q4. Answer: FDC SC	79.2 Percentage of HCPs	79.7 Percentage of HCPs	78.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q4. Answer: P+H IV	2.5 Percentage of HCPs	3.8 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q4. Answer: No Difference	12.6 Percentage of HCPs	12.7 Percentage of HCPs	12.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q4. Answer: Unsure	3.8 Percentage of HCPs	1.3 Percentage of HCPs	6.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q4. Answer: Missing	1.9 Percentage of HCPs	2.5 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q5. Answer: FDC SC	95.6 Percentage of HCPs	94.9 Percentage of HCPs	96.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q5. Answer: P+H IV	0.0 Percentage of HCPs	0.0 Percentage of HCPs	0.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q5. Answer: No Difference	2.5 Percentage of HCPs	2.5 Percentage of HCPs	2.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q5. Answer: Unsure	0.0 Percentage of HCPs	0.0 Percentage of HCPs	0.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q5. Answer: Missing	1.9 Percentage of HCPs	2.5 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q6. Answer: FDC SC	86.2 Percentage of HCPs	83.5 Percentage of HCPs	88.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q6. Answer: P+H IV	0.6 Percentage of HCPs	0.0 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q6. Answer: No Difference	11.3 Percentage of HCPs	13.9 Percentage of HCPs	8.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q6. Answer: Unsure	0.0 Percentage of HCPs	0.0 Percentage of HCPs	0.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q6. Answer: Missing	1.9 Percentage of HCPs	2.5 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q7. Answer: FDC SC	77.4 Percentage of HCPs	77.2 Percentage of HCPs	77.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q7. Answer: P+H IV	6.3 Percentage of HCPs	7.6 Percentage of HCPs	5.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q7. Answer: No Difference	2.5 Percentage of HCPs	2.5 Percentage of HCPs	2.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q7. Answer: Unsure	11.9 Percentage of HCPs	10.1 Percentage of HCPs	13.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room Q7. Answer: Missing	1.9 Percentage of HCPs	2.5 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 6 (each cycle is 21 days)

Population: The number analyzed includes HCPs who completed any part of the survey at treatment Cycle 6.

Healthcare professionals (HCPs) who administered study treatment responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Treatment Room Question 8: "How frequently would you offer or recommend FDC SC administration to your patients in the future?" The three available response options were: Always, Sometimes, and Never.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Percentage of Healthcare Professionals (HCPs) by Their Responses to Question 8 of the HCPQ - Treatment Room Always	67.3 Percentage of HCPs	69.6 Percentage of HCPs	65.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses to Question 8 of the HCPQ - Treatment Room Sometimes	30.2 Percentage of HCPs	26.6 Percentage of HCPs	33.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses to Question 8 of the HCPQ - Treatment Room Never	0.6 Percentage of HCPs	1.3 Percentage of HCPs	0.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses to Question 8 of the HCPQ - Treatment Room Missing	1.9 Percentage of HCPs	2.5 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycles 1-6 (each cycle is 21 days)

Population: The number analyzed includes healthcare professionals (HCPs) who completed question 1 of the survey per treatment cycle.

The Healthcare Professional Questionnaire (HCPQ)-Drug Preparation Room Question 1 was completed at each treatment cycle of the Treatment Cross-Over Period by the healthcare professionals (HCPs) within the pharmacy/drug preparation area where pertuzumab IV and trastuzumab IV and pertuzumab and trastuzumab FDC SC were prepared and dispensed for treating the study's participants. HCPs responded to the following question: "How long (in minutes) did it take to prepare the treatment for use?"

Outcome measures

Measure	All Participants n=80 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Duration of Treatment Preparation According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the HCPQ - Drug Preparation Room Cycle 1	20.0 minutes Interval 3.0 to 60.0	5.0 minutes Interval 1.0 to 50.0	—	—	—	—
Duration of Treatment Preparation According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the HCPQ - Drug Preparation Room Cycle 2	20.0 minutes Interval 3.0 to 60.0	5.0 minutes Interval 1.0 to 30.0	—	—	—	—
Duration of Treatment Preparation According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the HCPQ - Drug Preparation Room Cycle 3	17.5 minutes Interval 3.0 to 90.0	5.0 minutes Interval 1.0 to 40.0	—	—	—	—
Duration of Treatment Preparation According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the HCPQ - Drug Preparation Room Cycle 4	5.0 minutes Interval 1.0 to 30.0	15.0 minutes Interval 3.0 to 49.0	—	—	—	—
Duration of Treatment Preparation According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the HCPQ - Drug Preparation Room Cycle 5	5.0 minutes Interval 1.0 to 35.0	15.0 minutes Interval 3.0 to 50.0	—	—	—	—
Duration of Treatment Preparation According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the HCPQ - Drug Preparation Room Cycle 6	5.0 minutes Interval 1.0 to 40.0	15.0 minutes Interval 3.0 to 50.0	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 6 (each cycle is 21 days)

Population: The number analyzed includes healthcare professionals (HCPs) who completed any part of the survey at treatment Cycle 6.

Healthcare professionals (HCPs) who prepared study treatment within the pharmacy/drug preparation area responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Drug Preparation Room Question 2: "If all P+H IV infusions are switched to FDC SC injections, please indicate how strongly you agree or disagree with each of the following statements: a) Staff will have increased availability for other tasks in the pharmacy; b) Administrative procedures around FDC SC will require less time; c) FDC SC formulations will provide more flexibility for staff in managing their workload; d) Due to ready-to-use FDC SC formulations, potential dosing errors will be avoided; e) Due to ready-to-use FDC SC formulations, there will be less drug wastage; f) Without having to reconstitute the drug, less storage space for FDC SC related supplies will be required in the pharmacy; g) Preparation procedures and associated time staff time commitment will be reduced."

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement a): Strongly Disagree	1.3 Percentage of HCPs	1.3 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement a): Answer Missing	8.8 Percentage of HCPs	3.8 Percentage of HCPs	13.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement b): Strongly Disagree	5.6 Percentage of HCPs	8.8 Percentage of HCPs	2.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement b): Disagree	3.8 Percentage of HCPs	3.8 Percentage of HCPs	3.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement b): Neutral	14.4 Percentage of HCPs	16.3 Percentage of HCPs	12.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement b): Agree	18.1 Percentage of HCPs	17.5 Percentage of HCPs	18.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement b): Strongly Agree	46.3 Percentage of HCPs	46.3 Percentage of HCPs	46.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement b): Not Applicable	2.5 Percentage of HCPs	2.5 Percentage of HCPs	2.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement b): Answer Missing	9.4 Percentage of HCPs	5.0 Percentage of HCPs	13.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement c): Strongly Disagree	0.6 Percentage of HCPs	0.0 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement c): Disagree	0.6 Percentage of HCPs	0.0 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement a): Disagree	0.6 Percentage of HCPs	1.3 Percentage of HCPs	0.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement a): Neutral	7.5 Percentage of HCPs	8.8 Percentage of HCPs	6.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement a): Agree	28.8 Percentage of HCPs	28.8 Percentage of HCPs	28.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement a): Strongly Agree	50.6 Percentage of HCPs	52.5 Percentage of HCPs	48.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement a): Not Applicable	2.5 Percentage of HCPs	3.8 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement c): Neutral	13.1 Percentage of HCPs	15.0 Percentage of HCPs	11.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement c): Agree	26.3 Percentage of HCPs	28.8 Percentage of HCPs	23.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement c): Strongly Agree	48.8 Percentage of HCPs	50.0 Percentage of HCPs	47.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement c): Not Applicable	1.3 Percentage of HCPs	1.3 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement c): Answer Missing	9.4 Percentage of HCPs	5.0 Percentage of HCPs	13.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement d): Strongly Disagree	1.3 Percentage of HCPs	1.3 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement d): Disagree	3.8 Percentage of HCPs	1.3 Percentage of HCPs	6.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement d): Neutral	5.6 Percentage of HCPs	5.0 Percentage of HCPs	6.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement d): Agree	23.1 Percentage of HCPs	26.3 Percentage of HCPs	20.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement d): Strongly Agree	56.3 Percentage of HCPs	60.0 Percentage of HCPs	52.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement d): Not Applicable	1.3 Percentage of HCPs	1.3 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement d): Answer Missing	8.8 Percentage of HCPs	5.0 Percentage of HCPs	12.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement e): Strongly Disagree	1.3 Percentage of HCPs	1.3 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement e): Disagree	1.9 Percentage of HCPs	1.3 Percentage of HCPs	2.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement e): Neutral	8.8 Percentage of HCPs	11.3 Percentage of HCPs	6.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement e): Agree	21.9 Percentage of HCPs	21.3 Percentage of HCPs	22.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement e): Strongly Agree	55.0 Percentage of HCPs	58.8 Percentage of HCPs	51.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement e): Not Applicable	1.9 Percentage of HCPs	1.3 Percentage of HCPs	2.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement e): Answer Missing	9.4 Percentage of HCPs	5.0 Percentage of HCPs	13.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement f): Strongly Disagree	0.6 Percentage of HCPs	0.0 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement f): Disagree	4.4 Percentage of HCPs	3.8 Percentage of HCPs	5.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement f): Neutral	11.9 Percentage of HCPs	16.3 Percentage of HCPs	7.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement f): Agree	24.4 Percentage of HCPs	20.0 Percentage of HCPs	28.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement f): Strongly Agree	48.1 Percentage of HCPs	53.8 Percentage of HCPs	42.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement f): Not Applicable	1.3 Percentage of HCPs	1.3 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement f): Answer Missing	9.4 Percentage of HCPs	5.0 Percentage of HCPs	13.8 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement g): Strongly Disagree	0.6 Percentage of HCPs	0.0 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement g): Disagree	0.0 Percentage of HCPs	0.0 Percentage of HCPs	0.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement g): Neutral	6.9 Percentage of HCPs	8.8 Percentage of HCPs	5.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement g): Agree	31.3 Percentage of HCPs	30.0 Percentage of HCPs	32.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement g): Strongly Agree	48.8 Percentage of HCPs	52.5 Percentage of HCPs	45.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement g): Not Applicable	3.1 Percentage of HCPs	3.8 Percentage of HCPs	2.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room Statement g): Answer Missing	9.4 Percentage of HCPs	5.0 Percentage of HCPs	13.8 Percentage of HCPs	—	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 6 (each cycle is 21 days)

Population: The number analyzed includes healthcare professionals (HCPs) who completed any part of the survey at treatment Cycle 6.

Healthcare professionals (HCPs) who prepared study treatment within the pharmacy/drug preparation area responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Drug Preparation Room Questions 3 and 4: "Looking back over the Perjeta-Herceptin treatment sessions, please indicate based on your opinion which administration method: Q3. Was quickest from start to end of preparation to finish of administration (excluding observation period)?; Q4. Required less resource use for preparation and administration, for example nursing time, facility costs, equipment etc?" The three available response options were: P+H IV, FDC SC, and No Difference.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use of Each Study Regimen, Questions 3 and 4 of the HCPQ - Drug Preparation Room Q3. Answer: FDC SC	87.5 Percentage of HCPs	92.5 Percentage of HCPs	82.5 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use of Each Study Regimen, Questions 3 and 4 of the HCPQ - Drug Preparation Room Q3. Answer: P+H IV	0.6 Percentage of HCPs	0.0 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use of Each Study Regimen, Questions 3 and 4 of the HCPQ - Drug Preparation Room Q3. Answer: No Difference	1.3 Percentage of HCPs	1.3 Percentage of HCPs	1.3 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use of Each Study Regimen, Questions 3 and 4 of the HCPQ - Drug Preparation Room Q3. Answer: Missing	10.6 Percentage of HCPs	6.3 Percentage of HCPs	15.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use of Each Study Regimen, Questions 3 and 4 of the HCPQ - Drug Preparation Room Q4. Answer: FDC SC	86.9 Percentage of HCPs	93.8 Percentage of HCPs	80.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use of Each Study Regimen, Questions 3 and 4 of the HCPQ - Drug Preparation Room Q4. Answer: P+H IV	0.0 Percentage of HCPs	0.0 Percentage of HCPs	0.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use of Each Study Regimen, Questions 3 and 4 of the HCPQ - Drug Preparation Room Q4. Answer: No Difference	2.5 Percentage of HCPs	0.0 Percentage of HCPs	5.0 Percentage of HCPs	—	—	—
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use of Each Study Regimen, Questions 3 and 4 of the HCPQ - Drug Preparation Room Q4. Answer: Missing	10.6 Percentage of HCPs	6.3 Percentage of HCPs	15.0 Percentage of HCPs	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in Health-Related Quality of Life (HRQoL) as Assessed by the Global Health Status (GHS)/HRQoL Scale Score of the the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Baseline (BL): Value at Visit	74.21 score on a scale Standard Deviation 16.79	71.62 score on a scale Standard Deviation 17.98	76.77 score on a scale Standard Deviation 15.22	—	—	—
Change From Baseline Over Time in Health-Related Quality of Life (HRQoL) as Assessed by the Global Health Status (GHS)/HRQoL Scale Score of the the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Change from BL at Cycle 3 Day 1	0.27 score on a scale Standard Deviation 15.72	0.54 score on a scale Standard Deviation 16.63	0.00 score on a scale Standard Deviation 14.88	—	—	—
Change From Baseline Over Time in Health-Related Quality of Life (HRQoL) as Assessed by the Global Health Status (GHS)/HRQoL Scale Score of the the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Change from BL at Cycle 6 Day 1	-0.05 score on a scale Standard Deviation 18.38	1.10 score on a scale Standard Deviation 20.25	-1.16 score on a scale Standard Deviation 16.44	—	—	—
Change From Baseline Over Time in Health-Related Quality of Life (HRQoL) as Assessed by the Global Health Status (GHS)/HRQoL Scale Score of the the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Change from BL at Cycle 15 or Last Treatment Cycle	2.29 score on a scale Standard Deviation 17.05	2.82 score on a scale Standard Deviation 16.30	1.76 score on a scale Standard Deviation 17.87	—	—	—
Change From Baseline Over Time in Health-Related Quality of Life (HRQoL) as Assessed by the Global Health Status (GHS)/HRQoL Scale Score of the the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Change from BL at 1.5 Years	6.79 score on a scale Standard Deviation 19.38	7.18 score on a scale Standard Deviation 21.73	6.42 score on a scale Standard Deviation 16.92	—	—	—
Change From Baseline Over Time in Health-Related Quality of Life (HRQoL) as Assessed by the Global Health Status (GHS)/HRQoL Scale Score of the the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Change from BL at 2 Years	5.14 score on a scale Standard Deviation 18.45	6.16 score on a scale Standard Deviation 19.45	4.11 score on a scale Standard Deviation 17.46	—	—	—
Change From Baseline Over Time in Health-Related Quality of Life (HRQoL) as Assessed by the Global Health Status (GHS)/HRQoL Scale Score of the the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Change from BL at 3 Years	6.89 score on a scale Standard Deviation 18.45	7.23 score on a scale Standard Deviation 16.85	6.54 score on a scale Standard Deviation 20.12	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Physical Functioning Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	86.16 score on a scale Standard Deviation 14.48	84.22 score on a scale Standard Deviation 14.91	88.08 score on a scale Standard Deviation 13.86	—	—	—
Change From Baseline Over Time in the Physical Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	0.67 score on a scale Standard Deviation 12.08	1.77 score on a scale Standard Deviation 12.97	-0.42 score on a scale Standard Deviation 11.09	—	—	—
Change From Baseline Over Time in the Physical Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	1.20 score on a scale Standard Deviation 14.46	1.93 score on a scale Standard Deviation 16.61	0.51 score on a scale Standard Deviation 12.11	—	—	—
Change From Baseline Over Time in the Physical Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	2.54 score on a scale Standard Deviation 15.79	3.85 score on a scale Standard Deviation 13.65	1.22 score on a scale Standard Deviation 17.69	—	—	—
Change From Baseline Over Time in the Physical Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	4.74 score on a scale Standard Deviation 15.71	5.44 score on a scale Standard Deviation 17.29	4.05 score on a scale Standard Deviation 14.08	—	—	—
Change From Baseline Over Time in the Physical Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	3.97 score on a scale Standard Deviation 16.32	4.38 score on a scale Standard Deviation 18.57	3.56 score on a scale Standard Deviation 13.84	—	—	—
Change From Baseline Over Time in the Physical Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	2.51 score on a scale Standard Deviation 14.67	3.33 score on a scale Standard Deviation 13.99	1.64 score on a scale Standard Deviation 15.41	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Role Functioning Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	78.30 score on a scale Standard Deviation 25.76	79.54 score on a scale Standard Deviation 25.45	77.08 score on a scale Standard Deviation 26.17	—	—	—
Change From Baseline Over Time in the Role Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	6.71 score on a scale Standard Deviation 25.37	3.80 score on a scale Standard Deviation 24.01	9.58 score on a scale Standard Deviation 26.49	—	—	—
Change From Baseline Over Time in the Role Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	7.42 score on a scale Standard Deviation 26.12	6.36 score on a scale Standard Deviation 24.03	8.44 score on a scale Standard Deviation 28.10	—	—	—
Change From Baseline Over Time in the Role Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	9.62 score on a scale Standard Deviation 29.60	6.81 score on a scale Standard Deviation 24.00	12.44 score on a scale Standard Deviation 34.24	—	—	—
Change From Baseline Over Time in the Role Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	13.24 score on a scale Standard Deviation 30.00	9.49 score on a scale Standard Deviation 29.31	16.89 score on a scale Standard Deviation 30.41	—	—	—
Change From Baseline Over Time in the Role Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	11.30 score on a scale Standard Deviation 30.07	11.64 score on a scale Standard Deviation 29.22	10.96 score on a scale Standard Deviation 31.08	—	—	—
Change From Baseline Over Time in the Role Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	10.40 score on a scale Standard Deviation 29.13	8.09 score on a scale Standard Deviation 26.78	12.82 score on a scale Standard Deviation 31.43	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Emotional Functioning Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	82.08 score on a scale Standard Deviation 17.72	82.07 score on a scale Standard Deviation 16.99	82.08 score on a scale Standard Deviation 18.52	—	—	—
Change From Baseline Over Time in the Emotional Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	0.05 score on a scale Standard Deviation 15.92	-1.28 score on a scale Standard Deviation 15.26	1.35 score on a scale Standard Deviation 16.53	—	—	—
Change From Baseline Over Time in the Emotional Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	0.32 score on a scale Standard Deviation 18.70	0.99 score on a scale Standard Deviation 20.04	-0.32 score on a scale Standard Deviation 17.42	—	—	—
Change From Baseline Over Time in the Emotional Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	0.65 score on a scale Standard Deviation 19.60	-1.17 score on a scale Standard Deviation 15.77	2.46 score on a scale Standard Deviation 22.77	—	—	—
Change From Baseline Over Time in the Emotional Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	2.45 score on a scale Standard Deviation 22.47	0.93 score on a scale Standard Deviation 23.05	3.94 score on a scale Standard Deviation 21.95	—	—	—
Change From Baseline Over Time in the Emotional Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	1.86 score on a scale Standard Deviation 23.78	2.74 score on a scale Standard Deviation 21.61	0.99 score on a scale Standard Deviation 25.89	—	—	—
Change From Baseline Over Time in the Emotional Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	2.38 score on a scale Standard Deviation 23.78	3.55 score on a scale Standard Deviation 21.08	1.15 score on a scale Standard Deviation 26.43	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Cognitive Functioning Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	85.22 score on a scale Standard Deviation 18.37	85.86 score on a scale Standard Deviation 17.92	84.58 score on a scale Standard Deviation 18.90	—	—	—
Change From Baseline Over Time in the Cognitive Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	-0.95 score on a scale Standard Deviation 19.21	-0.64 score on a scale Standard Deviation 17.08	-1.25 score on a scale Standard Deviation 21.18	—	—	—
Change From Baseline Over Time in the Cognitive Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	-2.47 score on a scale Standard Deviation 20.44	-3.29 score on a scale Standard Deviation 18.86	-1.69 score on a scale Standard Deviation 21.94	—	—	—
Change From Baseline Over Time in the Cognitive Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	-4.69 score on a scale Standard Deviation 22.58	-7.75 score on a scale Standard Deviation 21.79	-1.64 score on a scale Standard Deviation 23.09	—	—	—
Change From Baseline Over Time in the Cognitive Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	-1.94 score on a scale Standard Deviation 21.31	-3.47 score on a scale Standard Deviation 20.16	-0.45 score on a scale Standard Deviation 22.41	—	—	—
Change From Baseline Over Time in the Cognitive Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	-1.03 score on a scale Standard Deviation 21.10	-2.51 score on a scale Standard Deviation 20.54	0.46 score on a scale Standard Deviation 21.69	—	—	—
Change From Baseline Over Time in the Cognitive Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	-3.01 score on a scale Standard Deviation 23.64	-2.45 score on a scale Standard Deviation 20.42	-3.59 score on a scale Standard Deviation 26.76	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=158 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=78 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Social Functioning Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	79.01 score on a scale Standard Deviation 21.79	77.99 score on a scale Standard Deviation 22.39	80.00 score on a scale Standard Deviation 21.28	—	—	—
Change From Baseline Over Time in the Social Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	6.26 score on a scale Standard Deviation 22.60	5.41 score on a scale Standard Deviation 24.40	7.08 score on a scale Standard Deviation 20.84	—	—	—
Change From Baseline Over Time in the Social Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	4.44 score on a scale Standard Deviation 22.87	6.44 score on a scale Standard Deviation 25.39	2.53 score on a scale Standard Deviation 20.16	—	—	—
Change From Baseline Over Time in the Social Functioning Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	7.80 score on a scale Standard Deviation 23.87	9.05 score on a scale Standard Deviation 23.86	6.57 score on a scale Standard Deviation 23.98	—	—	—
Change From Baseline Over Time in the Social Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	12.41 score on a scale Standard Deviation 24.20	12.21 score on a scale Standard Deviation 29.41	12.61 score on a scale Standard Deviation 18.05	—	—	—
Change From Baseline Over Time in the Social Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	13.68 score on a scale Standard Deviation 24.19	15.28 score on a scale Standard Deviation 25.29	12.10 score on a scale Standard Deviation 23.12	—	—	—
Change From Baseline Over Time in the Social Functioning Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	12.63 score on a scale Standard Deviation 24.46	11.94 score on a scale Standard Deviation 25.76	13.33 score on a scale Standard Deviation 23.24	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Fatigue Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	22.01 score on a scale Standard Deviation 18.90	24.47 score on a scale Standard Deviation 19.28	19.58 score on a scale Standard Deviation 18.31	—	—	—
Change From Baseline Over Time in the Fatigue Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	1.29 score on a scale Standard Deviation 16.35	-0.14 score on a scale Standard Deviation 17.66	2.71 score on a scale Standard Deviation 14.92	—	—	—
Change From Baseline Over Time in the Fatigue Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	0.50 score on a scale Standard Deviation 19.22	-3.22 score on a scale Standard Deviation 17.85	4.08 score on a scale Standard Deviation 19.91	—	—	—
Change From Baseline Over Time in the Fatigue Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	-2.11 score on a scale Standard Deviation 21.46	-3.44 score on a scale Standard Deviation 18.36	-0.78 score on a scale Standard Deviation 24.22	—	—	—
Change From Baseline Over Time in the Fatigue Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	-7.76 score on a scale Standard Deviation 19.59	-9.26 score on a scale Standard Deviation 20.43	-6.31 score on a scale Standard Deviation 18.76	—	—	—
Change From Baseline Over Time in the Fatigue Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	-5.25 score on a scale Standard Deviation 24.49	-6.54 score on a scale Standard Deviation 25.51	-3.96 score on a scale Standard Deviation 23.52	—	—	—
Change From Baseline Over Time in the Fatigue Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	-5.43 score on a scale Standard Deviation 22.58	-7.68 score on a scale Standard Deviation 21.66	-3.08 score on a scale Standard Deviation 23.45	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Nausea and Vomiting Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	2.73 score on a scale Standard Deviation 8.57	2.11 score on a scale Standard Deviation 7.24	3.33 score on a scale Standard Deviation 9.71	—	—	—
Change From Baseline Over Time in the Nausea and Vomiting Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	0.84 score on a scale Standard Deviation 10.74	0.21 score on a scale Standard Deviation 9.80	1.46 score on a scale Standard Deviation 11.62	—	—	—
Change From Baseline Over Time in the Nausea and Vomiting Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	0.75 score on a scale Standard Deviation 11.61	1.54 score on a scale Standard Deviation 11.92	0.00 score on a scale Standard Deviation 11.32	—	—	—
Change From Baseline Over Time in the Nausea and Vomiting Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	1.17 score on a scale Standard Deviation 11.34	1.88 score on a scale Standard Deviation 12.13	0.47 score on a scale Standard Deviation 10.53	—	—	—
Change From Baseline Over Time in the Nausea and Vomiting Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	-0.23 score on a scale Standard Deviation 11.41	0.46 score on a scale Standard Deviation 11.18	-0.90 score on a scale Standard Deviation 11.67	—	—	—
Change From Baseline Over Time in the Nausea and Vomiting Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	-0.68 score on a scale Standard Deviation 11.05	-0.23 score on a scale Standard Deviation 11.28	-1.14 score on a scale Standard Deviation 10.88	—	—	—
Change From Baseline Over Time in the Nausea and Vomiting Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	-0.75 score on a scale Standard Deviation 10.83	-1.23 score on a scale Standard Deviation 9.69	-0.26 score on a scale Standard Deviation 11.97	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Pain Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	0.43 score on a scale Standard Deviation 23.34	-2.41 score on a scale Standard Deviation 25.92	3.16 score on a scale Standard Deviation 20.34	—	—	—
Change From Baseline Over Time in the Pain Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	-1.17 score on a scale Standard Deviation 25.85	-2.82 score on a scale Standard Deviation 25.04	0.47 score on a scale Standard Deviation 26.72	—	—	—
Change From Baseline Over Time in the Pain Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	-1.26 score on a scale Standard Deviation 28.84	-1.62 score on a scale Standard Deviation 33.47	-0.90 score on a scale Standard Deviation 23.71	—	—	—
Change From Baseline Over Time in the Pain Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	-3.08 score on a scale Standard Deviation 26.91	-1.83 score on a scale Standard Deviation 30.25	-4.34 score on a scale Standard Deviation 23.25	—	—	—
Change From Baseline Over Time in the Pain Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	-2.13 score on a scale Standard Deviation 28.23	-1.72 score on a scale Standard Deviation 26.88	-2.56 score on a scale Standard Deviation 29.79	—	—	—
Change From Baseline Over Time in the Pain Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	16.04 score on a scale Standard Deviation 22.26	17.72 score on a scale Standard Deviation 24.94	14.38 score on a scale Standard Deviation 19.26	—	—	—
Change From Baseline Over Time in the Pain Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	0.21 score on a scale Standard Deviation 25.02	0.00 score on a scale Standard Deviation 27.86	0.42 score on a scale Standard Deviation 22.02	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Dyspnoea Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	5.87 score on a scale Standard Deviation 15.25	6.75 score on a scale Standard Deviation 15.45	5.00 score on a scale Standard Deviation 15.09	—	—	—
Change From Baseline Over Time in the Dyspnoea Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	0.63 score on a scale Standard Deviation 13.24	-0.42 score on a scale Standard Deviation 14.61	1.67 score on a scale Standard Deviation 11.74	—	—	—
Change From Baseline Over Time in the Dyspnoea Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	3.01 score on a scale Standard Deviation 15.83	1.32 score on a scale Standard Deviation 15.81	4.64 score on a scale Standard Deviation 15.77	—	—	—
Change From Baseline Over Time in the Dyspnoea Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	1.88 score on a scale Standard Deviation 17.65	1.41 score on a scale Standard Deviation 19.05	2.35 score on a scale Standard Deviation 16.26	—	—	—
Change From Baseline Over Time in the Dyspnoea Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	0.68 score on a scale Standard Deviation 13.82	-0.46 score on a scale Standard Deviation 10.46	1.80 score on a scale Standard Deviation 16.45	—	—	—
Change From Baseline Over Time in the Dyspnoea Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	1.83 score on a scale Standard Deviation 14.00	1.83 score on a scale Standard Deviation 16.56	1.83 score on a scale Standard Deviation 10.96	—	—	—
Change From Baseline Over Time in the Dyspnoea Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	1.50 score on a scale Standard Deviation 14.13	1.47 score on a scale Standard Deviation 13.42	1.54 score on a scale Standard Deviation 14.94	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Insomnia Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	22.22 score on a scale Standard Deviation 25.34	21.94 score on a scale Standard Deviation 24.97	22.50 score on a scale Standard Deviation 25.86	—	—	—
Change From Baseline Over Time in the Insomnia Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	1.26 score on a scale Standard Deviation 27.01	2.95 score on a scale Standard Deviation 26.25	-0.42 score on a scale Standard Deviation 27.81	—	—	—
Change From Baseline Over Time in the Insomnia Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	1.72 score on a scale Standard Deviation 29.86	5.26 score on a scale Standard Deviation 29.34	-1.69 score on a scale Standard Deviation 30.15	—	—	—
Change From Baseline Over Time in the Insomnia Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	-0.94 score on a scale Standard Deviation 31.75	3.76 score on a scale Standard Deviation 32.15	-5.63 score on a scale Standard Deviation 30.85	—	—	—
Change From Baseline Over Time in the Insomnia Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	-0.23 score on a scale Standard Deviation 30.95	1.85 score on a scale Standard Deviation 30.07	-2.25 score on a scale Standard Deviation 31.85	—	—	—
Change From Baseline Over Time in the Insomnia Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	2.97 score on a scale Standard Deviation 33.89	6.85 score on a scale Standard Deviation 35.56	-0.91 score on a scale Standard Deviation 31.90	—	—	—
Change From Baseline Over Time in the Insomnia Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	0.00 score on a scale Standard Deviation 34.08	1.47 score on a scale Standard Deviation 33.79	-1.54 score on a scale Standard Deviation 34.58	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Appetite Loss Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	10.06 score on a scale Standard Deviation 19.40	8.44 score on a scale Standard Deviation 14.59	11.67 score on a scale Standard Deviation 23.18	—	—	—
Change From Baseline Over Time in the Appetite Loss Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	0.21 score on a scale Standard Deviation 21.38	3.38 score on a scale Standard Deviation 23.02	-2.92 score on a scale Standard Deviation 19.26	—	—	—
Change From Baseline Over Time in the Appetite Loss Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	-0.86 score on a scale Standard Deviation 18.20	0.00 score on a scale Standard Deviation 18.86	-1.69 score on a scale Standard Deviation 17.62	—	—	—
Change From Baseline Over Time in the Appetite Loss Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	-5.40 score on a scale Standard Deviation 20.49	-4.69 score on a scale Standard Deviation 17.18	-6.10 score on a scale Standard Deviation 23.44	—	—	—
Change From Baseline Over Time in the Appetite Loss Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	-6.16 score on a scale Standard Deviation 19.96	-4.63 score on a scale Standard Deviation 20.41	-7.66 score on a scale Standard Deviation 19.54	—	—	—
Change From Baseline Over Time in the Appetite Loss Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	-4.34 score on a scale Standard Deviation 18.47	-5.48 score on a scale Standard Deviation 15.73	-3.20 score on a scale Standard Deviation 20.91	—	—	—
Change From Baseline Over Time in the Appetite Loss Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	-6.02 score on a scale Standard Deviation 19.61	-5.39 score on a scale Standard Deviation 15.89	-6.67 score on a scale Standard Deviation 22.97	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Constipation Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	9.01 score on a scale Standard Deviation 19.37	8.44 score on a scale Standard Deviation 16.42	9.58 score on a scale Standard Deviation 21.99	—	—	—
Change From Baseline Over Time in the Constipation Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	-1.68 score on a scale Standard Deviation 16.69	0.00 score on a scale Standard Deviation 15.10	-3.33 score on a scale Standard Deviation 18.06	—	—	—
Change From Baseline Over Time in the Constipation Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	-0.86 score on a scale Standard Deviation 19.35	0.88 score on a scale Standard Deviation 20.35	-2.53 score on a scale Standard Deviation 18.31	—	—	—
Change From Baseline Over Time in the Constipation Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	-0.70 score on a scale Standard Deviation 21.18	0.00 score on a scale Standard Deviation 20.31	-1.41 score on a scale Standard Deviation 22.14	—	—	—
Change From Baseline Over Time in the Constipation Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	0.23 score on a scale Standard Deviation 23.97	0.00 score on a scale Standard Deviation 17.69	0.45 score on a scale Standard Deviation 28.93	—	—	—
Change From Baseline Over Time in the Constipation Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	1.60 score on a scale Standard Deviation 26.93	5.94 score on a scale Standard Deviation 26.26	-2.74 score on a scale Standard Deviation 27.08	—	—	—
Change From Baseline Over Time in the Constipation Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	1.50 score on a scale Standard Deviation 23.52	0.49 score on a scale Standard Deviation 20.36	2.56 score on a scale Standard Deviation 26.55	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Diarrhoea Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	10.48 score on a scale Standard Deviation 21.59	12.24 score on a scale Standard Deviation 22.76	8.75 score on a scale Standard Deviation 20.36	—	—	—
Change From Baseline Over Time in the Diarrhoea Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	7.17 score on a scale Standard Deviation 27.22	4.70 score on a scale Standard Deviation 25.04	9.58 score on a scale Standard Deviation 29.14	—	—	—
Change From Baseline Over Time in the Diarrhoea Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	4.95 score on a scale Standard Deviation 24.26	4.39 score on a scale Standard Deviation 23.31	5.49 score on a scale Standard Deviation 25.28	—	—	—
Change From Baseline Over Time in the Diarrhoea Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	2.58 score on a scale Standard Deviation 26.06	2.82 score on a scale Standard Deviation 25.66	2.35 score on a scale Standard Deviation 26.62	—	—	—
Change From Baseline Over Time in the Diarrhoea Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	-6.39 score on a scale Standard Deviation 22.25	-8.33 score on a scale Standard Deviation 23.57	-4.50 score on a scale Standard Deviation 20.88	—	—	—
Change From Baseline Over Time in the Diarrhoea Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	-6.85 score on a scale Standard Deviation 23.79	-8.22 score on a scale Standard Deviation 26.52	-5.48 score on a scale Standard Deviation 20.80	—	—	—
Change From Baseline Over Time in the Diarrhoea Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	-7.52 score on a scale Standard Deviation 23.79	-9.80 score on a scale Standard Deviation 25.79	-5.13 score on a scale Standard Deviation 21.43	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)

Population: The Patient-Reported Outcome (PRO)-Evaluable Population includes all participants in the ITT population with a baseline EORTC QLQ-C30 assessment and at least one post-baseline EORTC QLQ-C30 assessment. The number analyzed at a given timepoint indicates participants with non-missing data at that timepoint.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater [worse] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Outcome measures

Measure	All Participants n=159 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=79 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Change From Baseline Over Time in the Financial Difficulties Scale Score of the EORTC QLQ-C30 Baseline (BL): Value at Visit	22.85 score on a scale Standard Deviation 27.59	23.63 score on a scale Standard Deviation 27.30	22.08 score on a scale Standard Deviation 28.04	—	—	—
Change From Baseline Over Time in the Financial Difficulties Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 3 Day 1	-2.95 score on a scale Standard Deviation 22.38	-2.99 score on a scale Standard Deviation 20.23	-2.92 score on a scale Standard Deviation 24.42	—	—	—
Change From Baseline Over Time in the Financial Difficulties Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 6 Day 1	-2.15 score on a scale Standard Deviation 22.69	-4.39 score on a scale Standard Deviation 20.61	0.00 score on a scale Standard Deviation 24.46	—	—	—
Change From Baseline Over Time in the Financial Difficulties Scale Score of the EORTC QLQ-C30 Change from BL at Cycle 15 or Last Treatment Cycle	-8.45 score on a scale Standard Deviation 25.24	-8.45 score on a scale Standard Deviation 25.02	-8.45 score on a scale Standard Deviation 25.65	—	—	—
Change From Baseline Over Time in the Financial Difficulties Scale Score of the EORTC QLQ-C30 Change from BL at 1.5 Years	-12.56 score on a scale Standard Deviation 28.27	-13.89 score on a scale Standard Deviation 30.00	-11.26 score on a scale Standard Deviation 26.62	—	—	—
Change From Baseline Over Time in the Financial Difficulties Scale Score of the EORTC QLQ-C30 Change from BL at 2 Years	-14.38 score on a scale Standard Deviation 27.93	-15.98 score on a scale Standard Deviation 27.84	-12.79 score on a scale Standard Deviation 28.13	—	—	—
Change From Baseline Over Time in the Financial Difficulties Scale Score of the EORTC QLQ-C30 Change from BL at 3 Years	-11.53 score on a scale Standard Deviation 30.99	-14.71 score on a scale Standard Deviation 32.26	-8.21 score on a scale Standard Deviation 29.48	—	—	—

SECONDARY outcome

Timeframe: From Day 1 of Cycle 1 to the end of Cycle 3 of Cross-Over Period; from Day 1 of Cycle 4 to the end of Cycle 6 of Cross-Over Period (1 cycle is 21 days)

Population: Safety Population: All participants who received at least one dose of any study treatment categorized according to the study treatment administered. In this analysis, participants are grouped by study arm and treatment received during the Cross-Over Period.

Investigators used the NCI CTCAE v4.0 grading scale for assessing adverse event (AE) severity; if not listed, AE severity was graded as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe or medically significant; Grade 4 = life-threatening; Grade 5 = death related to AE. Severity and seriousness are not synonymous and investigators independently assessed these criteria for each AE. Investigators also determined whether an AE was considered to be related to the study drug. Adverse events to monitor were defined based on known risks associated with the study drugs and included: hypersensitivity reactions, administration-related reactions (ARRs), cardiac dysfunction, diarrhea grade ≥3, rash/skin reactions, mucositis, interstitial lung disease (ILD), (febrile) neutropenia, pulmonary events that may occur as a result of an ARR, and pregnancy/neonatal related. Multiple occurrences of AEs were counted only once per participant. LVEF = left ventricular ejection fraction

Outcome measures

Measure	All Participants n=80 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) n=80 Participants This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Administration Related Reaction (ARR), Grade ≥3	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Cardiac Dysfunction AE, All Grades	2 Participants	1 Participants	3 Participants	3 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Cardiac Dysfunction AE, Grade ≥3	1 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Diarrhea Grade ≥3	0 Participants	0 Participants	1 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Rash/Skin Reactions	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Mucositis	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Pulmonary Events (ARR), All Grades	18 Participants	8 Participants	4 Participants	8 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Pulmonary Events (ARR), Grade ≥3	0 Participants	0 Participants	1 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Pregnancy and Neonatal Related AEs, All Grades	0 Participants	0 Participants	1 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Pregnancy and Neonatal Related AEs, Grade ≥3	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Interstitial Lung Disease (ILD)	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Neutropenia/Febrile Neutropenia, All Grades	4 Participants	1 Participants	2 Participants	3 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Neutropenia/Febrile Neutropenia, Grade ≥3	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Local Infusion Site Reaction	1 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Systemic Infusion Site Reaction	5 Participants	0 Participants	0 Participants	1 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Local Injection Site Reaction	0 Participants	12 Participants	24 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Systemic Injection Site Reaction	0 Participants	2 Participants	1 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received AE Leading to Any Study Treatment Discontinuation	0 Participants	1 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received AE Leading to PH FDC SC Discontinuation	0 Participants	1 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received AE Leading to Pertuzumab IV Discontinuation	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received AE Leading to Trastuzumab IV Discontinuation	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received AE Leading to Any Study Treatment Interruption or Dose Reduction	1 Participants	0 Participants	2 Participants	3 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Any Adverse Event (AE)	62 Participants	60 Participants	62 Participants	51 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received AE with Fatal Outcome	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Related AE with Fatal Outcome	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Grade 3 to 5 AE	1 Participants	1 Participants	3 Participants	4 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Related Grade 3 to 5 AE	1 Participants	0 Participants	1 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Cardiac AE (Including LVEF Events)	1 Participants	2 Participants	3 Participants	2 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Serious AE	1 Participants	1 Participants	1 Participants	5 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Anaphylaxis and Hypersensitivity AE, All Grades	0 Participants	2 Participants	1 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Anaphylaxis and Hypersensitivity AE, Grade ≥3	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received Administration Related Reaction (ARR), All Grades	7 Participants	14 Participants	24 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: From Day 1 of Cycle 1 to end of Cycle 6 of the Treatment Cross-Over Period; from Day 1 of Cycle 7 up to the completion of 18 cycles of neo/adjuvant anti-HER2 treatment in the Treatment Continuation Period (1 cycle is 21 days)

Population: Safety Population: All participants who received at least one dose of any study treatment categorized according to the study treatment administered. In this analysis, participants are grouped by treatment received during the Cross-Over and Continuation Periods.

Investigators used the NCI CTCAE v4.0 grading scale for assessing adverse event (AE) severity; if not listed, AE severity was graded as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe or medically significant; Grade 4 = life-threatening; Grade 5 = death related to AE. Severity and seriousness are not synonymous and investigators independently assessed these criteria for each AE. Investigators also determined whether an AE was considered to be related to the study drug. Adverse events to monitor were defined based on known risks associated with the study drugs and included: hypersensitivity reactions, administration-related reactions (ARRs), cardiac dysfunction, diarrhea grade ≥3, rash/skin reactions, mucositis, interstitial lung disease (ILD), (febrile) neutropenia, pulmonary events that may occur as a result of an ARR, and pregnancy/neonatal related. Multiple occurrences of AEs were counted only once per participant. LVEF = left ventricular ejection fraction

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=160 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=21 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) n=138 Participants This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Any Adverse Event (AE)	113 Participants	122 Participants	14 Participants	92 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods AE with Fatal Outcome	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Related AE with Fatal Outcome	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Grade 3 to 5 AE	5 Participants	4 Participants	2 Participants	7 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Related Grade 3 to 5 AE	1 Participants	1 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Cardiac AE (Including LVEF Events)	3 Participants	5 Participants	1 Participants	1 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Serious AE	6 Participants	2 Participants	0 Participants	4 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Anaphylaxis and Hypersensitivity AE, All Grades	0 Participants	3 Participants	0 Participants	2 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Anaphylaxis and Hypersensitivity AE, Grade ≥3	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Administration Related Reaction AE, All Grades	9 Participants	38 Participants	1 Participants	16 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Administration Related Reaction AE, Grade ≥3	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Cardiac Dysfunction AE, All Grades	5 Participants	4 Participants	1 Participants	2 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Cardiac Dysfunction AE, Grade ≥3	1 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Diarrhea Grade ≥3	0 Participants	1 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Rash/Skin Reactions	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Mucositis	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Pulmonary Events (ARR), All Grades	26 Participants	12 Participants	5 Participants	13 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Pulmonary Events (ARR), Grade ≥3	0 Participants	1 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Pregnancy and Neonatal Related AEs, All Grades	0 Participants	1 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Pregnancy and Neonatal Related AEs, Grade ≥3	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Interstitial Lung Disease (ILD), All Grades	0 Participants	0 Participants	0 Participants	1 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Interstitial Lung Disease (ILD), Grade ≥3	0 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Neutropenia/Febrile Neutropenia, All Grades	7 Participants	3 Participants	1 Participants	5 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Neutropenia/Febrile Neutropenia, Grade ≥3	0 Participants	0 Participants	0 Participants	1 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Local Infusion Site Reaction	1 Participants	0 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Systemic Infusion Site Reaction	6 Participants	0 Participants	1 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Local Injection Site Reaction	0 Participants	36 Participants	0 Participants	13 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods Systemic Injection Site Reaction	0 Participants	3 Participants	0 Participants	2 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods AE Leading to Any Study Treatment Discontinuation	0 Participants	1 Participants	1 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods AE Leading to PH FDC SC Discontinuation	0 Participants	1 Participants	0 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods AE Leading to Pertuzumab IV Discontinuation	0 Participants	0 Participants	1 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods AE Leading to Trastuzumab IV Discontinuation	0 Participants	0 Participants	1 Participants	0 Participants	—	—
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods AE Leading to Any Study Treatment Interruption or Dose Reduction	4 Participants	2 Participants	1 Participants	8 Participants	—	—

SECONDARY outcome

Timeframe: From Day 1 of Cycle 1 to end of Cycle 6 of the Treatment Cross-Over Period; from Day 1 of Cycle 7 up to the completion of 18 cycles of neo/adjuvant anti-HER2 treatment in the Treatment Continuation Period (1 cycle is 21 days)

Population: Safety Population: All participants who received at least one dose of any study treatment categorized according to the study treatment administered. In this analysis, participants are grouped by treatment received during the Cross-Over and Continuation Periods.

Heart failure is defined as a disorder characterized by the inability of the heart to pump blood at an adequate volume to meet tissue metabolic requirements, or, the ability to do only at an elevation in the filling pressure. Any adverse event of symptomatic left ventricular systolic dysfunction (LVSD; also referred to as heart failure) occurring during the study was to be reported as a serious adverse event.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=160 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=21 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) n=138 Participants This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Number of Participants With at Least One Event of Heart Failure With the FDC SC and IV Formulations During the Treatment Cross-Over and Treatment Continuation Periods	0 Participants	0 Participants	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Baseline; Day 1 of Cycles 4, 7, and 11 (each cycle is 21 days); End of Treatment Visit (up to 1 year)

Population: Safety Population: All participants who received at least one dose of any study treatment categorized according to the study treatment administered. In this analysis, participants are grouped by treatment received during the Cross-Over and Continuation Periods.

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. All participants who enrolled in this study must have had a baseline LVEF ≥55%. Verbatim description of adverse events was mapped to Medical Dictionary for Regulatory Activities (MedDRA) version 25.1. The MedDRA preferred term of 'ejection fraction decreased' is defined as an LVEF decrease of at least 10 percentage points from baseline and to below 50%.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=160 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=21 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) n=138 Participants This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Number of Participants With at Least One Event of Ejection Fraction Decreased With the FDC SC and IV Formulations During the Treatment Cross-Over and Treatment Continuation Periods	3 Participants	4 Participants	1 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Pre-dose at Day 1 of Cycles 1 (baseline), 4, and 7, and end of treatment (up to 18 cycles; 1 cycle is 21 days)

Population: Safety Population: All participants who received at least one dose of any study treatment categorized according to the study treatment administered. In this analysis, participants are grouped by study arm and treatment received during the Cross-Over Period, and only by treatment received during the Continuation Period. The number analyzed (denominator) represents those without an abnormality at baseline.

The number of participants at any post-baseline timepoint with abnormal readings outside the normal range for vital signs of diastolic and systolic blood pressure, pulse rate, respiratory rate, and body temperature were summarized according the specified direction of the abnormal reading (high or low). The number analyzed (denominator) in the results table represents participants without the specified abnormal vital sign at baseline. Not every vital sign abnormality qualified as an adverse event (AE). A vital sign result must have been reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption, or treatment discontinuation); resulted in a medical intervention or a change in concomitant therapy; or, was clinically significant in the investigator's judgment.

Outcome measures

Measure	All Participants n=80 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) n=80 Participants This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period n=21 Participants This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period n=138 Participants This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Number of Participants With Targeted Vital Signs Outside the Normal Limits Among Those Without an Abnormality at Baseline During the Treatment Cross-Over and Treatment Continuation Periods Diastolic Blood Pressure - Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Targeted Vital Signs Outside the Normal Limits Among Those Without an Abnormality at Baseline During the Treatment Cross-Over and Treatment Continuation Periods Diastolic Blood Pressure - High	2 Participants	2 Participants	0 Participants	0 Participants	0 Participants	3 Participants
Number of Participants With Targeted Vital Signs Outside the Normal Limits Among Those Without an Abnormality at Baseline During the Treatment Cross-Over and Treatment Continuation Periods Systolic Blood Pressure - Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Targeted Vital Signs Outside the Normal Limits Among Those Without an Abnormality at Baseline During the Treatment Cross-Over and Treatment Continuation Periods Systolic Blood Pressure - High	8 Participants	7 Participants	3 Participants	3 Participants	1 Participants	12 Participants
Number of Participants With Targeted Vital Signs Outside the Normal Limits Among Those Without an Abnormality at Baseline During the Treatment Cross-Over and Treatment Continuation Periods Pulse Rate - Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Targeted Vital Signs Outside the Normal Limits Among Those Without an Abnormality at Baseline During the Treatment Cross-Over and Treatment Continuation Periods Pulse Rate - High	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Targeted Vital Signs Outside the Normal Limits Among Those Without an Abnormality at Baseline During the Treatment Cross-Over and Treatment Continuation Periods Respiratory Rate - Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Targeted Vital Signs Outside the Normal Limits Among Those Without an Abnormality at Baseline During the Treatment Cross-Over and Treatment Continuation Periods Respiratory Rate - High	1 Participants	0 Participants	2 Participants	2 Participants	0 Participants	4 Participants
Number of Participants With Targeted Vital Signs Outside the Normal Limits Among Those Without an Abnormality at Baseline During the Treatment Cross-Over and Treatment Continuation Periods Temperature - Low	22 Participants	17 Participants	10 Participants	13 Participants	4 Participants	34 Participants
Number of Participants With Targeted Vital Signs Outside the Normal Limits Among Those Without an Abnormality at Baseline During the Treatment Cross-Over and Treatment Continuation Periods Temperature - High	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dose at Day 1 of Cycles 1 (baseline), 4, 7, 11, 15, and end of treatment (up to 18 cycles; 1 cycle is 21 days)

Population: Safety Population: All participants who received at least one dose of any study treatment categorized according to the study treatment administered. In this analysis, participants are grouped by study arm and treatment received during the Cross-Over Period. The number analyzed (denominator) represents those with NCI-CTCAE Grade 0-2 at baseline and at least one post-baseline assessment.

Laboratory data for targeted chemistry and hematology parameters were classified according to the NCI CTCAE v4.0; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). The results show the shifts in the number of participants with Grade 0-2 at baseline to Grade 3-4 post-baseline; those with missing baseline values were counted as Grade 0-2 at baseline. Not every laboratory abnormality qualified as an adverse event, only if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption, or treatment discontinuation); resulted in a medical intervention or a change in concomitant therapy; or, was clinically significant in the investigator's judgment. SGOT/AST = aspartate aminotransferase; SGPT/ALT = alanine aminotransferase

Outcome measures

Measure	All Participants n=80 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) n=80 Participants This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period n=21 Participants This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period n=138 Participants This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods Neutrophils, Total, Abs - Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods Platelet - Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods Total Leukocyte Count - Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods Total Leukocyte Count - High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods Alkaline Phosphatase - High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods SGPT/ALT - High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods SGOT/AST - High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods Creatinine - High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods Bilirubin, Total - High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods Hemoglobin - Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods Hemoglobin - High	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 3 years, 10 months

Population: ITT Population

Overall survival (OS) is defined as the time from randomization to death due to any cause. The number of participants who had an OS event (i.e., died) while on study is reported.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Number of Participants With an Event for Overall Survival, Overall and by Treatment Sequence	2 Participants	2 Participants	0 Participants	—	—	—

SECONDARY outcome

Timeframe: At 12, 24, and 36 months

Population: ITT Population; the number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an overall survival event.

Overall survival is defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization +1 day. Kaplan-Meier methodology was used to estimate the percentage of participants who were alive (event-free) at 12, 24, and 36 months.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Overall Survival, Overall and by Treatment Sequence 12 Months	100.00 Percentage of participants Interval 100.0 to 100.0	100.00 Percentage of participants Interval 100.0 to 100.0	100.00 Percentage of participants Interval 100.0 to 100.0	—	—	—
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Overall Survival, Overall and by Treatment Sequence 24 Months	99.36 Percentage of participants Interval 98.12 to 100.0	98.73 Percentage of participants Interval 96.27 to 100.0	100.00 Percentage of participants Interval 100.0 to 100.0	—	—	—
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Overall Survival, Overall and by Treatment Sequence 36 Months	98.71 Percentage of participants Interval 96.92 to 100.0	97.44 Percentage of participants Interval 93.93 to 100.0	100.00 Percentage of participants Interval 100.0 to 100.0	—	—	—

SECONDARY outcome

Timeframe: Up to 3 years, 10 months

Population: ITT Population

Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Second primary non-breast invasive cancer (with the exception of non-melanoma skin cancers and in situ carcinoma of any site) was included as an event.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Number of Participants With an Event for Invasive Disease-Free Survival Including Second Primary Non-Breast Cancer, Overall and by Treatment Sequence	12 Participants	7 Participants	5 Participants	—	—	—

SECONDARY outcome

Timeframe: At 12, 24, and 36 months

Population: ITT Population; the number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an invasive-disease free survival (including second primary non-breast cancer) event.

Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Second primary non-breast invasive cancer (with the exception of non-melanoma skin cancers and in situ carcinoma of any site) was included as an event. Participants who had not experienced invasive disease at the time of analysis were censored: i) at the time of the last clinical breast examination if they had post-baseline clinical breast examination; ii) on the date of randomization +1 day if no post-baseline clinical breast examination. Kaplan-Meier methodology was used to estimate the percentage of participants who were event-free at 12, 24, and 36 months.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Invasive Disease-Free Survival Including Second Primary Non-Breast Cancer, Overall and by Treatment Sequence 12 Months	97.46 Percentage of participants Interval 95.0 to 99.92	94.94 Percentage of participants Interval 90.1 to 99.77	100.00 Percentage of participants Interval 100.0 to 100.0	—	—	—
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Invasive Disease-Free Survival Including Second Primary Non-Breast Cancer, Overall and by Treatment Sequence 24 Months	94.87 Percentage of participants Interval 91.4 to 98.33	92.37 Percentage of participants Interval 86.5 to 98.24	97.38 Percentage of participants Interval 93.8 to 100.0	—	—	—
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Invasive Disease-Free Survival Including Second Primary Non-Breast Cancer, Overall and by Treatment Sequence 36 Months	93.53 Percentage of participants Interval 89.65 to 97.41	91.05 Percentage of participants Interval 84.72 to 97.38	96.03 Percentage of participants Interval 91.63 to 100.0	—	—	—

SECONDARY outcome

Timeframe: Up to 3 years, 10 months

Population: ITT Population

Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) were not counted as recurrence.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Number of Participants With an Event for Invasive Disease-Free Survival, Overall and by Treatment Sequence	11 Participants	6 Participants	5 Participants	—	—	—

SECONDARY outcome

Timeframe: At 12, 24, and 36 months

Population: ITT Population; the number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an invasive-disease free survival event.

Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) were not counted as recurrence. Participants who had not experienced invasive disease at the time of analysis were censored: i) at the time of the last clinical breast examination if they had post-baseline clinical breast examination; ii) on the date of randomization +1 day if no post-baseline clinical breast examination. Kaplan-Meier methodology was used to estimate the percentage of participants who were event-free at 12, 24, and 36 months.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Invasive Disease-Free Survival, Overall and by Treatment Sequence 12 Months	98.10 Percentage of participants Interval 95.96 to 100.0	96.20 Percentage of participants Interval 91.99 to 100.0	100.00 Percentage of participants Interval 100.0 to 100.0	—	—	—
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Invasive Disease-Free Survival, Overall and by Treatment Sequence 24 Months	95.51 Percentage of participants Interval 92.25 to 98.76	93.64 Percentage of participants Interval 88.24 to 99.03	97.38 Percentage of participants Interval 93.8 to 100.0	—	—	—
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Invasive Disease-Free Survival, Overall and by Treatment Sequence 36 Months	94.17 Percentage of participants Interval 90.47 to 97.87	92.32 Percentage of participants Interval 86.41 to 98.23	96.03 Percentage of participants Interval 91.63 to 100.0	—	—	—

SECONDARY outcome

Timeframe: Up to 3 years, 10 months

Population: ITT Population

Distant disease-free survival (DDFS) is defined as the time from randomization to the date of distant breast cancer recurrence (i.e., evidence of breast cancer in any anatomic site other than for ipsilateral [loco-regional] invasive breast cancer recurrence that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer).

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Number of Participants With an Event for Distant Disease-Free Survival, Overall and by Treatment Sequence	9 Participants	5 Participants	4 Participants	—	—	—

SECONDARY outcome

Timeframe: At 12, 24, and 36 months

Population: ITT Population; the number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for a distant disease-free survival event.

Distant disease-free survival (DDFS) is defined as the time from randomization to the date of distant breast cancer recurrence (i.e., evidence of breast cancer in any anatomic site other than for ipsilateral [loco-regional] invasive breast cancer recurrence that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer). Participants who had not experienced invasive disease at the time of analysis were censored: i) at the time of the last clinical breast examination if they had post-baseline clinical breast examination; ii) on the date of randomization +1 day if no post-baseline clinical breast examination. Kaplan-Meier methodology was used to estimate the percentage of participants who were event-free at 12, 24, and 36 months.

Outcome measures

Measure	All Participants n=160 Participants In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	A: P+H IV Followed by PH FDC SC n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	B: PH FDC SC Followed by P+H IV n=80 Participants In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.	Arm B: Treatment With P+H IV (Cycles 4 to 6) This safety analysis population only includes adverse events that occurred in Arm B participants during treatment Cycles 4 to 6 when all Arm B participants were treated with P+H IV. In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received treatment with pertuzumab and trastuzumab FDC SC (PH FDC SC) for 3 treatment cycles and that was followed by treatment with pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles (1 cycle = 21 days).	P+H IV: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination administered subcutaneously (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Distant Disease-Free Survival, Overall and by Treatment Sequence 12 Months	98.73 Percentage of participants Interval 96.98 to 100.0	97.47 Percentage of participants Interval 94.0 to 100.0	100.00 Percentage of participants Interval 100.0 to 100.0	—	—	—
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Distant Disease-Free Survival, Overall and by Treatment Sequence 24 Months	96.14 Percentage of participants Interval 93.11 to 99.17	94.90 Percentage of participants Interval 90.04 to 99.77	97.38 Percentage of participants Interval 93.8 to 100.0	—	—	—
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Distant Disease-Free Survival, Overall and by Treatment Sequence 36 Months	94.80 Percentage of participants Interval 91.3 to 98.31	93.58 Percentage of participants Interval 88.14 to 99.03	96.03 Percentage of participants Interval 91.63 to 100.0	—	—	—

Adverse Events

P+H IV: Treatment Cross-Over Period

Serious events: 6 serious events

Other events: 62 other events

Deaths: 0 deaths

PH FDC SC: Treatment Cross-Over Period

Serious events: 2 serious events

Other events: 84 other events

Deaths: 0 deaths

P+H IV: Treatment Continuation Period

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

PH FDC SC: Treatment Continuation Period

Serious events: 4 serious events

Other events: 47 other events

Deaths: 0 deaths

All Participants: All Study Treatment Periods

Serious events: 11 serious events

Other events: 125 other events

Deaths: 0 deaths

Follow-Up Period

Serious events: 1 serious events

Other events: 2 other events

Deaths: 2 deaths

Serious adverse events

Measure	P+H IV: Treatment Cross-Over Period n=160 participants at risk This safety analysis population includes all participants from Arms A and B who received up to 3 cycles (1 cycle = 21 days) of treatment with pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Cross-Over Period of the study.	PH FDC SC: Treatment Cross-Over Period n=160 participants at risk This safety analysis population includes all participants from Arms A and B who received up to 3 cycles (1 cycle = 21 days) of treatment with the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) during the Treatment Cross-Over Period of the study.	P+H IV: Treatment Continuation Period n=21 participants at risk This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period n=138 participants at risk This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	All Participants: All Study Treatment Periods n=160 participants at risk This safety analysis population includes all participants from Arms A and B who received at least one dose of treatment with pertuzumab IV and trastuzumab IV (P+H IV) and/or the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) across any of the treatment periods during the study from first dose through 28 days after the last dose of study treatment.	Follow-Up Period n=159 participants at risk This safety analysis population includes all participants from Arms A and B who had received at least one dose of any study treatment and had not discontinued from the study prior to entering the follow-up period. The timeframe of the follow-up period started at 29 days after the last dose of study treatment until the end of follow-up (≥3 years after randomization of the last participant).
Infections and infestations Device related infection	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.72% 1/138 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	1.2% 2/160 • Number of events 2 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Infections and infestations Erysipelas	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	1.4% 2/138 • Number of events 2 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	1.2% 2/160 • Number of events 3 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Infections and infestations Breast cellulitis	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/138 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Infections and infestations Bronchopulmonary aspergillosis	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.72% 1/138 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Infections and infestations Pneumonia	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/138 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Infections and infestations Upper respiratory tract infection	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/138 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Investigations Ejection fraction decreased	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/138 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	1.2% 2/160 • Number of events 2 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/138 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Infections and infestations COVID-19	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.72% 1/138 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Cardiac disorders Cardiac failure	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/138 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.63% 1/159 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.

Other adverse events

Measure	P+H IV: Treatment Cross-Over Period n=160 participants at risk This safety analysis population includes all participants from Arms A and B who received up to 3 cycles (1 cycle = 21 days) of treatment with pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Cross-Over Period of the study.	PH FDC SC: Treatment Cross-Over Period n=160 participants at risk This safety analysis population includes all participants from Arms A and B who received up to 3 cycles (1 cycle = 21 days) of treatment with the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) during the Treatment Cross-Over Period of the study.	P+H IV: Treatment Continuation Period n=21 participants at risk This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	PH FDC SC: Treatment Continuation Period n=138 participants at risk This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).	All Participants: All Study Treatment Periods n=160 participants at risk This safety analysis population includes all participants from Arms A and B who received at least one dose of treatment with pertuzumab IV and trastuzumab IV (P+H IV) and/or the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) across any of the treatment periods during the study from first dose through 28 days after the last dose of study treatment.	Follow-Up Period n=159 participants at risk This safety analysis population includes all participants from Arms A and B who had received at least one dose of any study treatment and had not discontinued from the study prior to entering the follow-up period. The timeframe of the follow-up period started at 29 days after the last dose of study treatment until the end of follow-up (≥3 years after randomization of the last participant).
Gastrointestinal disorders Diarrhoea	10.6% 17/160 • Number of events 20 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	9.4% 15/160 • Number of events 19 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	19.0% 4/21 • Number of events 4 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	10.9% 15/138 • Number of events 23 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	23.1% 37/160 • Number of events 66 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
General disorders Fatigue	5.0% 8/160 • Number of events 8 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	5.6% 9/160 • Number of events 10 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	4.8% 1/21 • Number of events 3 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	5.1% 7/138 • Number of events 8 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	11.9% 19/160 • Number of events 29 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
General disorders Injection site reaction	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	22.5% 36/160 • Number of events 50 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	9.4% 13/138 • Number of events 28 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	27.5% 44/160 • Number of events 78 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Injury, poisoning and procedural complications Radiation skin injury	16.9% 27/160 • Number of events 29 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	10.6% 17/160 • Number of events 17 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.72% 1/138 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	27.5% 44/160 • Number of events 47 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Musculoskeletal and connective tissue disorders Arthralgia	3.8% 6/160 • Number of events 8 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	5.0% 8/160 • Number of events 9 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	14.3% 3/21 • Number of events 3 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	4.3% 6/138 • Number of events 6 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	14.4% 23/160 • Number of events 26 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.63% 1/159 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/160 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	9.5% 2/21 • Number of events 2 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/138 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	1.2% 2/160 • Number of events 2 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Musculoskeletal and connective tissue disorders Myalgia	3.8% 6/160 • Number of events 6 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	1.9% 3/160 • Number of events 3 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	9.5% 2/21 • Number of events 2 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.72% 1/138 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	7.5% 12/160 • Number of events 12 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.63% 1/159 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Nervous system disorders Headache	1.9% 3/160 • Number of events 3 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	3.1% 5/160 • Number of events 6 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	9.5% 2/21 • Number of events 3 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.72% 1/138 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	6.2% 10/160 • Number of events 13 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Skin and subcutaneous tissue disorders Rash	1.2% 2/160 • Number of events 3 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	1.9% 3/160 • Number of events 3 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	14.3% 3/21 • Number of events 3 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	1.4% 2/138 • Number of events 3 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	6.2% 10/160 • Number of events 12 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Vascular disorders Hot flush	3.8% 6/160 • Number of events 6 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	5.6% 9/160 • Number of events 10 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	2.2% 3/138 • Number of events 3 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	10.0% 16/160 • Number of events 19 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Musculoskeletal and connective tissue disorders Pain in extremity	0.62% 1/160 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	2.5% 4/160 • Number of events 5 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	9.5% 2/21 • Number of events 2 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	2.9% 4/138 • Number of events 5 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	5.6% 9/160 • Number of events 13 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.63% 1/159 • Number of events 1 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.
Skin and subcutaneous tissue disorders Pruritus	4.4% 7/160 • Number of events 8 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	1.9% 3/160 • Number of events 3 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/21 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	5.1% 7/138 • Number of events 7 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	8.8% 14/160 • Number of events 18 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.	0.00% 0/159 • AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years). After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but only after the first publication or presentation that involves the overall study. The Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER