A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 (HER2)-Positive Primary Breast Cancer (APHINITY)

• ClinicalTrials.gov Identifier: NCT01358877
• Recruitment Status: Active, not recruiting
• First Posted: May 24, 2011
• Results First Posted: January 5, 2018
• Last Update Posted: April 10, 2024
• Sponsor: Hoffmann-La Roche
• Collaborators: Genentech, Inc.; Breast International Group
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Breast Cancer
• Interventions: Drug: 5-Fluorouracil; Drug: Carboplatin; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Doxorubicin; Drug: Epirubicin; Drug: Paclitaxel; Drug: Pertuzumab; Drug: Placebo; Drug: Trastuzumab
• Enrollment: 4804

Participant Flow

Recruitment Details
Pre-assignment Details	The analysis included data up to a clinical data cut-off date of 19 December 2016.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) intravenously (IV) every 3 weeks (Q3W) for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 once weekly (QW); 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 milligrams per kilogram [mg/kg] loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 milligrams per square meter (mg/m^2) + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 milligrams [mg]).
Period Title: Overall Study
Started	2400	2404
Did Not Receive Study Drug	22	13
Received Study Drug (Safety Population)	2364 [1]	2405 [2]
Completed	0	0
Not Completed	2400	2404
Reason Not Completed
Death	80	89
Ongoing follow-up for post-recurrence	87	108
Ongoing follow-up for IDFS event	2084	2073
Ongoing follow-up for overall survival	7	5
Other	142	129
[1] 24 placebo participants received at least 1 dose of pertuzumab and were included in pertuzumab arm.; [2] 38 pertuzumab participants did not receive pertuzumab and were included in placebo arm.

Baseline Characteristics

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy	Total
Arm/Group Description		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).	Total of all reporting groups
Overall Number of Baseline Participants		2400	2404	4804
Baseline Analysis Population Description		Intent-to-treat (ITT) population included all randomized participants regardless of treatment received.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	2400 participants	2404 participants	4804 participants
		51.7 (10.9)	51.4 (10.7)	51.5 (10.8)
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2400 participants	2404 participants	4804 participants
	Female	2397 99.9%	2396 99.7%	4793 99.8%
	Male	3 0.1%	8 0.3%	11 0.2%
		[1] Measure Analysis Population Description: ITT population

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Invasive Disease-Free Survival (IDFS) Event (Excluding Second Primary Non-Breast Cancer [SPNBC]), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
Description	Percentage of participants with IDFS events (excluding SPNBC) is reported. IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (that is [i.e.], an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including ductal carcinoma in situ [DCIS] and lobular carcinoma in situ [LCIS]) and non-melanoma skin cancer were excluded as an event.
Time Frame	Randomization to the first occurrence of IDFS event (excluding SPNBC) (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2400	2404
Measure Type: Number; Unit of Measure: percentage of participants
	7.1	8.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Analysis was performed using stratified log-rank test, which included nodal status, protocol version, central hormone receptor status, and adjuvant chemotherapy regimen as stratification factors in the randomization.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0446
	Comments	Statistical significance was controlled at a two-sided alpha level of 0.05.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.66 to 1.00
	Estimation Comments	Hazard ratio was estimated by Cox regression.

2. Primary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Excluding SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
Description	Kaplan-Meier estimate of the percentage of participants who were IDFS event-free (excluding SPNBC) at Year 3 is reported. IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including DCIS and LCIS) and non-melanoma skin cancer were excluded as an event.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

ITT population. Overall number of participants analyzed=participants remaining at risk for IDFS event (excluding SPNBC) at Year 3.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2101	2108
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Estimate of percentage of participants
	94.06; (93.09 to 95.03)	93.24; (92.21 to 94.26)

3. Secondary Outcome

Title	Percentage of Participants With IDFS Event (Including SPNBC), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
Description	Percentage of participants with IDFS events (including SPNBC) is reported. IDFS-SPNBC event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).
Time Frame	Randomization to the first occurrence of IDFS event (including SPNBC) (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2400	2404
Measure Type: Number; Unit of Measure: percentage of participants
	7.9	9.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Analysis was performed using stratified log-rank test, which included nodal status, protocol version, central hormone receptor status, and adjuvant chemotherapy regimen as stratification factors in the randomization.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0430
	Comments	Statistical significance was controlled at a two-sided alpha level of 0.05.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.68 to 0.99
	Estimation Comments	Hazard ratio was estimated by Cox regression.

4. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Including SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
Description	Kaplan-Meier estimate of the percentage of participants who were IDFS event-free (including SPNBC) at Year 3 is reported. IDFS-SPNBC was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

ITT population. Overall number of participants analyzed=participants remaining at risk for IDFS event (including SPNBC) at Year 3.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2093	2095
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Estimate of percentage of participants
	93.50; (92.49 to 94.51)	92.51; (91.43 to 93.58)

5. Secondary Outcome

Title	Percentage of Participants With Disease-Free Survival (DFS) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
Description	Percentage of participants with DFS event is reported. DFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC or contralateral or ipsilateral DCIS.
Time Frame	Randomization to the first occurrence of DFS event (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2400	2404
Measure Type: Number; Unit of Measure: percentage of participants
	8.0	9.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Analysis was performed using stratified log-rank test, which included nodal status, protocol version, central hormone receptor status, and adjuvant chemotherapy regimen as stratification factors in the randomization.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0327
	Comments	Statistical significance was controlled at a two-sided alpha level of 0.05.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.67 to 0.98
	Estimation Comments	Hazard ratio was estimated by Cox regression.

6. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Were DFS Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
Description	Kaplan-Meier estimate of the percentage of participants who were DFS event-free at Year 3 is reported. DFS was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC or contralateral or ipsilateral DCIS.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

ITT population. Overall number of participants analyzed=participants remaining at risk for DFS event at Year 3.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2091	2090
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Estimate of percentage of participants
	93.42; (92.40 to 94.43)	92.29; (91.21 to 93.38)

7. Secondary Outcome

Title	Percentage of Participants Who Died
Description	Percentage of participants who died due to any cause is reported.
Time Frame	Randomization until death due to any cause (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2400	2404
Measure Type: Number; Unit of Measure: percentage of participants
	3.3	3.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Analysis was performed using stratified log-rank test, which included nodal status, protocol version, central hormone receptor status, and adjuvant chemotherapy regimen as stratification factors in the randomization.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4673
	Comments	Statistical significance was controlled at a two-sided alpha level of 0.05.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.66 to 1.21
	Estimation Comments	Hazard ratio was estimated by Cox regression.

8. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Were Alive at Year 3
Description	The Kaplan-Meier approach was used to estimate the percentage of participants who were alive at 3 years.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

ITT population. Overall number of participants analyzed=participants remaining at risk for death at Year 3.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2186	2209
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Estimate of percentage of participants
	97.65; (97.03 to 98.27)	97.67; (97.06 to 98.29)

9. Secondary Outcome

Title	Percentage of Participants With Recurrence-Free Interval (RFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
Description	Percentage of participants with RFI event is reported. RFI event was defined as local, regional or distant breast cancer recurrence.
Time Frame	Randomization until local, regional or distant breast cancer recurrence (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2400	2404
Measure Type: Number; Unit of Measure: percentage of participants
	5.8	7.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Analysis was performed using stratified log-rank test, which included nodal status, protocol version, central hormone receptor status, and adjuvant chemotherapy regimen as stratification factors in the randomization.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0430
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.63 to 0.99
	Estimation Comments	Hazard ratio was estimated by Cox regression.

10. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Were RFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
Description	Kaplan-Meier estimate of the percentage of participants who were RFI event-free at Year 3 is reported. RFI event was defined as local, regional or distant breast cancer recurrence.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

ITT population. Overall number of participants analyzed=participants remaining at risk for RFI event at Year 3.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2116	2129
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Estimate of percentage of participants
	95.18; (94.30 to 96.06)	94.27; (93.32 to 95.21)

11. Secondary Outcome

Title	Percentage of Participants With Distant Recurrence-Free Interval (DRFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
Description	Percentage of participants with DRFI event is reported. DRFI event was defined as distant breast cancer recurrence.
Time Frame	Randomization until distant breast cancer recurrence (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2400	2404
Measure Type: Number; Unit of Measure: percentage of participants
	5.0	6.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	Analysis was performed using stratified log-rank test, which included nodal status, protocol version, central hormone receptor status, and adjuvant chemotherapy regimen as stratification factors in the randomization.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1007
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.04
	Estimation Comments	Hazard ratio was estimated by Cox regression.

12. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Were DRFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
Description	Kaplan-Meier estimate of the percentage of participants who were DRFI event-free at Year 3 is reported. DRFI event was defined as distant breast cancer recurrence.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

ITT population. Overall number of participants analyzed=participants remaining at risk for DRFI event at Year 3.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2126	2145
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Estimate of percentage of participants
	95.70; (94.86 to 96.53)	95.13; (94.25 to 96.00)

13. Secondary Outcome

Title	Percentage of Participants With Primary Cardiac Event
Description	Primary cardiac event was defined as either: Heart Failure (New York Heart Association [NYHA] Class III or IV) and a drop in left ventricular ejection fraction (LVEF) of at least 10 ejection fraction (EF) points from baseline and to below 50 percent (%); or cardiac death. Cardiac death was defined as either definite cardiac death: due to heart failure, myocardial infarction, or documented primary arrhythmia; or probable cardiac death: sudden unexpected death within 24 hours of a definite or probable cardiac event (e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia) without documented etiology.
Time Frame	Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)

Outcome Measure Data

Analysis Population Description

Safety population included participants who received any amount of study medication (chemotherapy, pertuzumab/placebo, or trastuzumab), according to the treatment actually received.

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2364	2405
Measure Type: Number; Unit of Measure: percentage of participants
Primary Cardiac Event (Composite)	0.7	0.3
Heart Failure and LVEF Decline	0.6	0.2
Cardiac Death (Definite or Probable)	0.1	0.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; 0.0 to 0.8
	Estimation Comments	The difference in percentage of participants with a primary cardiac event between the pertuzumab and placebo arms. The 95% confidence interval (CI) was estimated using Hauck-Anderson correction.

14. Secondary Outcome

Title	Percentage of Participants With Secondary Cardiac Event
Description	Secondary cardiac event was defined as asymptomatic or mildly symptomatic (NYHA Class II) significant drop in LVEF (defined as an absolute decrease of at least 10 EF points from baseline and to below 50%), confirmed by a second LVEF assessment within approximately three weeks of the first significant LVEF assessment or confirmed by the Cardiac Advisory Board (CAB).
Time Frame	Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed	2364	2405
Measure Type: Number; Unit of Measure: percentage of participants
	2.7	2.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.9
	Estimation Comments	95% CI was estimated using Hauck-Anderson correction.

15. Secondary Outcome

Title	Change From Baseline in LVEF to Worst Post-Baseline Value
Description	LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. Baseline LVEF value and the maximum absolute decrease (worst value) in LVEF measurement from baseline were reported. LVEF was measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan.
Time Frame	Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)

Outcome Measure Data

Analysis Population Description

Safety population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed=participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		2363	2401
Mean (Standard Deviation); Unit of Measure: percentage of blood pumped out
Baseline	Number Analyzed	2363 participants	2401 participants
		65.2 (5.9)	65.3 (6.1)
Change to Worst Value	Number Analyzed	2348 participants	2351 participants
		-7.5 (6.6)	-7.6 (6.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.5
	Estimation Comments	95% CI was estimated using Hauck-Anderson correction.

16. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Scale Score
Description	EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall quality of life (QOL) in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, used 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 global scores were linearly transformed on a scale of 0 to 100, with a high score indicating better GHS/QOL. Negative change from Baseline values indicated deterioration in QOL or functioning and positive values indicated improvement.
Time Frame	Baseline, Weeks 13, 25; end of treatment (EOT, 28 days after the last dose, up to Week 56); Follow-up (FU) Months 18, 24, 36

Outcome Measure Data

Analysis Population Description

ITT population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed=number of participants responding to this scale where it is considered complete as defined by the EORTC QLQ-C30 scoring manual.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		2329	2338
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	Number Analyzed	2329 participants	2338 participants
		72.9 (19.7)	72.5 (19.7)
Change at Week 13	Number Analyzed	2065 participants	2110 participants
		-11.2 (22.8)	-10.2 (22.6)
Change at Week 25	Number Analyzed	2035 participants	2073 participants
		-4.4 (21.6)	-2.9 (21.0)
Change at EOT	Number Analyzed	2254 participants	2282 participants
		-3.1 (21.9)	-1.1 (21.8)
Change at FU Month 18	Number Analyzed	1906 participants	1918 participants
		1.9 (21.5)	1.3 (22.2)
Change at FU Month 24	Number Analyzed	1861 participants	1866 participants
		2.2 (22.1)	2.4 (22.1)
Change at FU Month 36	Number Analyzed	1811 participants	1782 participants
		2.8 (21.4)	1.8 (22.5)

17. Secondary Outcome

Title	Change From Baseline in EORTC QLQ-C30 Functioning Subscale Scores
Description	EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, N/V, constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 functioning scores were linearly transformed on a scale of 0 to 100, with a high score indicating better functioning/support. Negative change from Baseline values indicated deterioration in functioning and positive values indicated improvement.
Time Frame	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

Outcome Measure Data

Analysis Population Description

ITT population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed=number of participants responding to this scale where it is considered complete as defined by the EORTC QLQ-C30 scoring manual.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		2338	2342
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline: Physical	Number Analyzed	2338 participants	2342 participants
		89.6 (12.9)	89.1 (13.4)
Change at Week 13: Physical	Number Analyzed	2077 participants	2115 participants
		-10.7 (17.2)	-10.6 (17.7)
Change at Week 25: Physical	Number Analyzed	2052 participants	2078 participants
		-4.6 (14.5)	-4.3 (14.5)
Change at EOT: Physical	Number Analyzed	2262 participants	2287 participants
		-4.1 (14.7)	-3.2 (14.9)
Change at FU Month 18: Physical	Number Analyzed	1918 participants	1925 participants
		-0.9 (13.5)	-0.9 (14.5)
Change at FU Month 24: Physical	Number Analyzed	1867 participants	1875 participants
		-0.4 (13.8)	-0.3 (14.5)
Change at FU Month 36: Physical	Number Analyzed	1820 participants	1792 participants
		-0.3 (14.1)	-0.1 (13.9)
Baseline: Role	Number Analyzed	2334 participants	2337 participants
		79.8 (24.7)	79.4 (25.2)
Change at Week 13: Role	Number Analyzed	2075 participants	2111 participants
		-8.0 (28.6)	-8.5 (29.5)
Change at Week 25: Role	Number Analyzed	2049 participants	2073 participants
		-0.7 (26.4)	0.4 (27.8)
Change at EOT: Role	Number Analyzed	2258 participants	2281 participants
		0.4 (27.8)	2.3 (28.1)
Change at FU Month 18: Role	Number Analyzed	1916 participants	1921 participants
		6.1 (26.5)	5.7 (28.9)
Change at FU Month 24: Role	Number Analyzed	1865 participants	1872 participants
		7.3 (26.8)	6.9 (28.2)
Change at FU Month 36: Role	Number Analyzed	1817 participants	1790 participants
		7.9 (26.4)	7.6 (27.9)
Baseline: Social	Number Analyzed	2332 participants	2336 participants
		81.9 (22.9)	80.6 (24.1)
Change at Week 13: Social	Number Analyzed	2071 participants	2110 participants
		-8.7 (25.8)	-7.8 (27.1)
Change at Week 25: Social	Number Analyzed	2044 participants	2072 participants
		-2.2 (24.5)	-0.7 (26.3)
Change at EOT: Social	Number Analyzed	2258 participants	2282 participants
		0.0 (25.2)	1.2 (26.3)
Change at FU Month 18: Social	Number Analyzed	1910 participants	1915 participants
		5.0 (23.8)	4.8 (26.7)
Change at FU Month 24: Social	Number Analyzed	1864 participants	1868 participants
		5.5 (24.8)	6.5 (26.6)
Change at FU Month 36: Social	Number Analyzed	1812 participants	1783 participants
		6.6 (24.9)	7.1 (27.3)
Baseline: Cognitive	Number Analyzed	2334 participants	2341 participants
		88.8 (16.6)	87.9 (17.9)
Change at Week 13: Cognitive	Number Analyzed	2073 participants	2115 participants
		-9.1 (20.5)	-9.0 (21.4)
Change at Week 25: Cognitive	Number Analyzed	2046 participants	2076 participants
		-7.6 (20.4)	-7.0 (20.8)
Change at EOT: Cognitive	Number Analyzed	2259 participants	2287 participants
		-7.7 (20.6)	-7.2 (21.4)
Change at FU Month 18: Cognitive	Number Analyzed	1911 participants	1920 participants
		-6.1 (19.6)	-5.8 (21.2)
Change at FU Month 24: Cognitive	Number Analyzed	1865 participants	1870 participants
		-6.2 (20.5)	-5.5 (21.7)
Change at FU Month 36: Cognitive	Number Analyzed	1814 participants	1786 participants
		-5.4 (20.6)	-4.9 (21.8)
Baseline: Emotional	Number Analyzed	2332 participants	2340 participants
		72.8 (22.4)	71.3 (22.7)
Change at Week 13: Emotional	Number Analyzed	2071 participants	2114 participants
		3.3 (22.2)	2.9 (22.5)
Change at Week 25: Emotional	Number Analyzed	2044 participants	2076 participants
		5.1 (22.7)	5.9 (22.2)
Change at EOT: Emotional	Number Analyzed	2257 participants	2286 participants
		5.6 (23.2)	6.2 (23.4)
Change at FU Month 18: Emotional	Number Analyzed	1909 participants	1918 participants
		7.7 (23.4)	7.6 (23.4)
Change at FU Month 24: Emotional	Number Analyzed	1864 participants	1869 participants
		7.8 (23.3)	8.5 (24.2)
Change at FU Month 36: Emotional	Number Analyzed	1812 participants	1785 participants
		7.8 (23.8)	8.4 (24.4)

18. Secondary Outcome

Title	Change From Baseline in EORTC QLQ-C30 Disease/Treatment-Related Symptoms Subscale Scores
Description	EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 disease/treatment-related symptom scores were linearly transformed on a scale of 0 to 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicated improvement in symptoms and positive values indicated worsening of symptoms.
Time Frame	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

Outcome Measure Data

Analysis Population Description

ITT population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed=number of participants responding to this scale where it is considered complete as defined by the EORTC QLQ-C30 scoring manual.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		2338	2342
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline: Diarrhea	Number Analyzed	2329 participants	2339 participants
		5.2 (14.4)	5.1 (13.5)
Change at Week 13: Diarrhea	Number Analyzed	2067 participants	2111 participants
		22.3 (29.8)	9.2 (23.9)
Change at Week 25: Diarrhea	Number Analyzed	2043 participants	2075 participants
		13.2 (26.5)	3.3 (19.8)
Change at EOT: Diarrhea	Number Analyzed	2257 participants	2285 participants
		12.2 (26.9)	2.9 (20.0)
Change at FU Month 18: Diarrhea	Number Analyzed	1907 participants	1919 participants
		-0.5 (17.7)	0.2 (17.5)
Change at FU Month 24: Diarrhea	Number Analyzed	1861 participants	1868 participants
		-0.8 (17.4)	0.2 (18.3)
Change at FU Month 36: Diarrhea	Number Analyzed	1810 participants	1784 participants
		-0.8 (16.5)	0.3 (16.9)
Baseline: Fatigue	Number Analyzed	2335 participants	2341 participants
		22.4 (19.7)	23.2 (20.5)
Change at Week 13: Fatigue	Number Analyzed	2074 participants	2116 participants
		16.1 (24.3)	16.2 (24.4)
Change at Week 25: Fatigue	Number Analyzed	2050 participants	2078 participants
		7.8 (22.5)	6.6 (22.3)
Change at EOT: Fatigue	Number Analyzed	2259 participants	2287 participants
		7.1 (23.0)	5.2 (23.0)
Change at FU Month 18: Fatigue	Number Analyzed	1914 participants	1924 participants
		1.1 (21.7)	1.2 (22.5)
Change at FU Month 24: Fatigue	Number Analyzed	1864 participants	1873 participants
		0.4 (22.0)	0.4 (22.6)
Change at FU Month 36: Fatigue	Number Analyzed	1817 participants	1791 participants
		-0.2 (21.8)	0.6 (22.8)
Baseline: Dyspnea	Number Analyzed	2331 participants	2336 participants
		6.8 (15.5)	8.0 (17.1)
Change at Week 13: Dyspnea	Number Analyzed	2067 participants	2112 participants
		12.3 (23.8)	14.6 (26.4)
Change at Week 25: Dyspnea	Number Analyzed	2045 participants	2073 participants
		6.3 (19.9)	6.4 (22.1)
Change at EOT: Dyspnea	Number Analyzed	2254 participants	2283 participants
		6.6 (20.5)	6.5 (22.5)
Change at FU Month 18: Dyspnea	Number Analyzed	1911 participants	1917 participants
		5.9 (21.0)	5.0 (21.5)
Change at FU Month 24: Dyspnea	Number Analyzed	1860 participants	1870 participants
		5.1 (20.5)	5.3 (22.4)
Change at FU Month 36: Dyspnea	Number Analyzed	1814 participants	1783 participants
		5.1 (20.5)	5.3 (22.3)
Baseline: Appetite Loss	Number Analyzed	2335 participants	2340 participants
		8.5 (18.2)	9.1 (18.7)
Change at Week 13: Appetite Loss	Number Analyzed	2073 participants	2114 participants
		13.6 (29.2)	7.7 (27.9)
Change at Week 25: Appetite Loss	Number Analyzed	2049 participants	2078 participants
		5.2 (25.1)	0.3 (22.4)
Change at EOT: Appetite Loss	Number Analyzed	2257 participants	2286 participants
		3.0 (24.5)	-0.9 (22.6)
Change at FU Month 18: Appetite Loss	Number Analyzed	1913 participants	1924 participants
		-3.0 (20.1)	-3.1 (21.1)
Change at FU Month 24: Appetite Loss	Number Analyzed	1862 participants	1871 participants
		-3.2 (20.6)	-3.3 (21.0)
Change at FU Month 36: Appetite Loss	Number Analyzed	1817 participants	1789 participants
		-3.0 (20.4)	-2.7 (21.2)
Baseline: Insomnia	Number Analyzed	2333 participants	2338 participants
		25.3 (27.4)	27.3 (28.5)
Change at Week 13: Insomnia	Number Analyzed	2073 participants	2111 participants
		6.3 (30.3)	5.1 (32.2)
Change at Week 25: Insomnia	Number Analyzed	2049 participants	2073 participants
		4.3 (30.6)	2.0 (31.8)
Change at EOT: Insomnia	Number Analyzed	2257 participants	2282 participants
		3.2 (31.0)	0.9 (32.8)
Change at FU Month 18: Insomnia	Number Analyzed	1913 participants	1917 participants
		-0.1 (31.1)	0.4 (32.4)
Change at FU Month 24: Insomnia	Number Analyzed	1863 participants	1869 participants
		-1.5 (31.3)	-1.1 (32.9)
Change at FU Month 36: Insomnia	Number Analyzed	1816 participants	1786 participants
		-0.3 (31.1)	-0.5 (33.5)
Baseline: N/V	Number Analyzed	2338 participants	2342 participants
		2.7 (8.2)	3.1 (9.4)
Change at Week 13: N/V	Number Analyzed	2077 participants	2118 participants
		5.6 (15.7)	3.7 (14.5)
Change at Week 25: N/V	Number Analyzed	2052 participants	2079 participants
		1.1 (11.8)	0.5 (12.4)
Change at EOT: N/V	Number Analyzed	2261 participants	2288 participants
		1.6 (12.7)	0.8 (13.2)
Change at FU Month 18: N/V	Number Analyzed	1918 participants	1925 participants
		-0.2 (10.5)	-0.4 (12.1)
Change at FU Month 24: N/V	Number Analyzed	1865 participants	1874 participants
		0.0 (10.7)	-0.1 (11.8)
Change at FU Month 36: N/V	Number Analyzed	1819 participants	1792 participants
		0.3 (11.0)	0.2 (11.7)
Baseline: Constipation	Number Analyzed	2335 participants	2339 participants
		8.7 (19.1)	10.0 (19.8)
Change at Week 13: Constipation	Number Analyzed	2066 participants	2113 participants
		1.4 (23.5)	4.1 (25.6)
Change at Week 25: Constipation	Number Analyzed	2047 participants	2075 participants
		-0.7 (21.8)	0.2 (22.8)
Change at EOT: Constipation	Number Analyzed	2256 participants	2285 participants
		0.1 (22.4)	0.9 (23.3)
Change at FU Month 18: Constipation	Number Analyzed	1912 participants	1922 participants
		3.0 (23.3)	1.5 (23.8)
Change at FU Month 24: Constipation	Number Analyzed	1865 participants	1872 participants
		2.1 (23.1)	0.6 (22.9)
Change at FU Month 36: Constipation	Number Analyzed	1815 participants	1784 participants
		2.1 (22.9)	1.5 (22.7)
Baseline: Pain	Number Analyzed	2337 participants	2342 participants
		18.8 (21.4)	19.6 (22.1)
Change at Week 13: Pain	Number Analyzed	2077 participants	2118 participants
		2.3 (25.4)	5.0 (26.1)
Change at Week 25: Pain	Number Analyzed	2051 participants	2080 participants
		1.4 (24.1)	1.4 (24.9)
Change at EOT: Pain	Number Analyzed	2261 participants	2288 participants
		0.1 (24.7)	0.5 (25.8)
Change at FU Month 18: Pain	Number Analyzed	1918 participants	1927 participants
		-1.3 (23.3)	-0.5 (25.8)
Change at FU Month 24: Pain	Number Analyzed	1868 participants	1874 participants
		-1.6 (24.2)	-2.2 (25.6)
Change at FU Month 36: Pain	Number Analyzed	1818 participants	1792 participants
		-2.6 (24.4)	-2.3 (25.0)

19. Secondary Outcome

Title	Change From Baseline in EORTC QLQ-C30 Financial Difficulties Subscale Scores
Description	EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, N/V, constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 financial difficulties scores were linearly transformed on a scale of 0 and 100, with a high score indicating a higher level of financial difficulties. Negative change from Baseline values indicated improvement in financial difficulties and positive values indicated worsening of financial difficulties.
Time Frame	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

Outcome Measure Data

Analysis Population Description

ITT population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed=number of participants responding to this scale where it is considered complete as defined by the EORTC QLQ-C30 scoring manual.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		2319	2334
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	Number Analyzed	2319 participants	2334 participants
		20.3 (28.7)	22.1 (30.0)
Change at Week 13	Number Analyzed	2052 participants	2103 participants
		3.1 (26.1)	1.7 (27.0)
Change at Week 25	Number Analyzed	2025 participants	2067 participants
		2.3 (26.8)	-0.3 (26.9)
Change at EOT	Number Analyzed	2244 participants	2280 participants
		-0.2 (27.6)	-1.5 (27.2)
Change at FU Month 18	Number Analyzed	1894 participants	1912 participants
		-4.1 (27.9)	-5.1 (27.5)
Change at FU Month 24	Number Analyzed	1852 participants	1866 participants
		-5.2 (28.6)	-6.9 (29.3)
Change at FU Month 36	Number Analyzed	1798 participants	1781 participants
		-7.1 (28.5)	-8.3 (28.3)

20. Secondary Outcome

Title	Change From Baseline in European Organisation for Research and Treatment of Cancer - Breast Cancer Module Quality of Life (EORTC QLQ-BR23) Functional Scale Score
Description	EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL.
Time Frame	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

Outcome Measure Data

Analysis Population Description

ITT population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed=participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		2313	2318
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline: Body Image	Number Analyzed	2313 participants	2317 participants
		79.7 (23.5)	78.9 (23.7)
Change at Week 13: Body Image	Number Analyzed	2048 participants	2086 participants
		-12.9 (24.7)	-13.9 (25.2)
Change at Week 25: Body Image	Number Analyzed	2020 participants	2050 participants
		-7.6 (23.8)	-7.3 (23.4)
Change at EOT: Body Image	Number Analyzed	2237 participants	2261 participants
		-4.9 (23.7)	-6.0 (24.6)
Change at FU Month 18: Body Image	Number Analyzed	1887 participants	1889 participants
		-0.1 (23.3)	-1.3 (23.3)
Change at FU Month 24: Body Image	Number Analyzed	1839 participants	1852 participants
		0.5 (23.6)	0.1 (23.5)
Change at FU Month 36: Body Image	Number Analyzed	1789 participants	1758 participants
		1.7 (24.4)	0.7 (24.6)
Baseline: Sexual Enjoyment	Number Analyzed	966 participants	997 participants
		54.0 (30.8)	55.0 (30.7)
Change at Week 13: Sexual Enjoyment	Number Analyzed	530 participants	553 participants
		-16.5 (28.4)	-13.1 (27.2)
Change at Week 25: Sexual Enjoyment	Number Analyzed	558 participants	630 participants
		-11.9 (26.8)	-7.9 (26.5)
Change at EOT: Sexual Enjoyment	Number Analyzed	781 participants	820 participants
		-10.7 (27.5)	-8.0 (27.7)
Change at FU Month 18: Sexual Enjoyment	Number Analyzed	585 participants	581 participants
		-4.2 (28.5)	-6.7 (26.5)
Change at FU Month 24: Sexual Enjoyment	Number Analyzed	576 participants	561 participants
		-6.0 (28.4)	-5.0 (27.6)
Change at FU Month 36: Sexual Enjoyment	Number Analyzed	530 participants	541 participants
		-5.3 (28.1)	-6.0 (26.8)
Baseline: Sexual Function	Number Analyzed	2258 participants	2260 participants
		19.6 (23.8)	20.8 (24.3)
Change at Week 13: Sexual Function	Number Analyzed	1969 participants	2008 participants
		-5.6 (20.5)	-6.6 (20.7)
Change at Week 25: Sexual Function	Number Analyzed	1945 participants	1975 participants
		-2.6 (20.8)	-2.3 (20.9)
Change at EOT: Sexual Function	Number Analyzed	2176 participants	2191 participants
		-1.0 (20.8)	-1.4 (21.2)
Change at FU Month 18: Sexual Function	Number Analyzed	1814 participants	1820 participants
		2.5 (22.8)	1.4 (21.7)
Change at FU Month 24: Sexual Function	Number Analyzed	1757 participants	1778 participants
		2.8 (22.9)	1.8 (22.7)
Change at FU Month 36: Sexual Function	Number Analyzed	1711 participants	1685 participants
		2.6 (24.0)	1.6 (23.6)
Baseline: FP	Number Analyzed	2312 participants	2318 participants
		51.3 (31.7)	50.5 (31.5)
Change at Week 13: FP	Number Analyzed	2043 participants	2090 participants
		3.1 (30.2)	1.8 (31.9)
Change at Week 25: FP	Number Analyzed	2020 participants	2052 participants
		6.3 (31.1)	5.4 (31.2)
Change at EOT: FP	Number Analyzed	2238 participants	2263 participants
		7.7 (32.2)	6.9 (31.8)
Change at FU Month 18: FP	Number Analyzed	1887 participants	1884 participants
		12.9 (32.0)	10.5 (32.0)
Change at FU Month 24 : FP	Number Analyzed	1836 participants	1849 participants
		13.7 (32.9)	12.9 (32.9)
Change at FU Month 36: FP	Number Analyzed	1785 participants	1752 participants
		14.7 (34.1)	13.6 (32.9)

21. Secondary Outcome

Title	Change From Baseline in EORTC QLQ-BR23 Symptom Scale Score
Description	EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for symptom scale indicated high level of symptomatology/problems/greater degree of symptoms. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL.
Time Frame	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

Outcome Measure Data

Analysis Population Description

ITT population. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed=participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		2331	2335
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline:Systemic SE	Number Analyzed	2331 participants	2335 participants
		9.5 (10.9)	10.2 (11.2)
Change at Week 13: Systemic SE	Number Analyzed	2071 participants	2107 participants
		21.1 (17.5)	21.7 (17.9)
Change at Week 25: Systemic SE	Number Analyzed	2043 participants	2072 participants
		9.2 (14.2)	8.2 (14.2)
Change at EOT: Systemic SE	Number Analyzed	2258 participants	2280 participants
		8.3 (15.4)	7.5 (14.8)
Change at FU Month 18: Systemic SE	Number Analyzed	1909 participants	1912 participants
		4.4 (12.8)	5.5 (13.4)
Change at FU Month 24: Systemic SE	Number Analyzed	1860 participants	1871 participants
		4.1 (13.2)	4.9 (13.7)
Change at FU Month 36: Systemic SE	Number Analyzed	1812 participants	1783 participants
		4.5 (13.6)	5.2 (13.8)
Baseline: Hair Loss	Number Analyzed	356 participants	340 participants
		26.4 (32.8)	22.1 (29.0)
Change at Week 13: Hair Loss	Number Analyzed	208 participants	206 participants
		17.3 (43.6)	21.2 (37.8)
Change at Week 25: Hair Loss	Number Analyzed	100 participants	101 participants
		8.3 (38.0)	14.5 (38.4)
Change at EOT: Hair Loss	Number Analyzed	297 participants	290 participants
		10.9 (40.1)	17.9 (39.8)
Change at FU Month 18: Hair Loss	Number Analyzed	71 participants	104 participants
		-7.0 (36.0)	3.2 (34.9)
Change at FU Month 24: Hair Loss	Number Analyzed	73 participants	92 participants
		-4.1 (39.3)	0.7 (36.0)
Change at FU Month 36: Hair Loss	Number Analyzed	95 participants	111 participants
		-5.6 (42.3)	2.4 (34.7)
Baseline: Arm Symptoms	Number Analyzed	2326 participants	2331 participants
		21.6 (19.1)	21.7 (19.2)
Change at Week 13: Arm Symptoms	Number Analyzed	2064 participants	2102 participants
		-4.7 (20.8)	-2.1 (21.5)
Change at Week 25: Arm Symptoms	Number Analyzed	2037 participants	2070 participants
		-2.9 (21.3)	-2.3 (21.7)
Change at EOT: Arm Symptoms	Number Analyzed	2251 participants	2275 participants
		-3.5 (21.5)	-3.4 (21.4)
Change at FU Month 18: Arm Symptoms	Number Analyzed	1903 participants	1913 participants
		-4.0 (21.8)	-3.9 (22.5)
Change at FU Month 24: Arm Symptoms	Number Analyzed	1857 participants	1866 participants
		-5.1 (21.6)	-5.0 (22.3)
Change at FU Month 36: Arm Symptoms	Number Analyzed	1809 participants	1777 participants
		-5.9 (21.8)	-4.7 (22.4)
Baseline: Breast Symptoms	Number Analyzed	2325 participants	2330 participants
		19.5 (17.5)	20.4 (17.7)
Change at Week 13: Breast Symptoms	Number Analyzed	2063 participants	2102 participants
		-5.0 (18.4)	-5.2 (18.0)
Change at Week 25: Breast Symptoms	Number Analyzed	2036 participants	2069 participants
		1.9 (20.7)	-0.4 (20.6)
Change at EOT: Breast Symptoms	Number Analyzed	2250 participants	2275 participants
		-0.6 (20.2)	-3.8 (19.7)
Change at FU Month 18: Breast Symptoms	Number Analyzed	1903 participants	1911 participants
		-3.0 (18.7)	-5.9 (18.8)
Change at FU Month 24: Breast Symptoms	Number Analyzed	1857 participants	1865 participants
		-6.4 (18.4)	-7.3 (18.7)
Change at FU Month 36: Breast Symptoms	Number Analyzed	1808 participants	1775 participants
		-7.3 (18.8)	-7.9 (19.0)

22. Secondary Outcome

Title	Percentage of Participants With Response for European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Domain
Description	EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in mobility domain was reported: I have no problems in walking about; I have some problems in walking about; and I am confined to bed. Response percentages may not add up to 100% due to data rounding.
Time Frame	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

Outcome Measure Data

Analysis Population Description

ITT population. Number analyzed=participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		2400	2404
Measure Type: Number; Unit of Measure: percentage of participants
Baseline: No problems	Number Analyzed	2292 participants	2310 participants
		93.8	92.9
Baseline: Some problems	Number Analyzed	2292 participants	2310 participants
		6.2	6.9
Baseline: Confined to bed	Number Analyzed	2292 participants	2310 participants
		0.0	0.2
Week 13: No problems	Number Analyzed	2080 participants	2129 participants
		77.5	74.8
Week 13: Some problems	Number Analyzed	2080 participants	2129 participants
		22.1	24.8
Week 13: Confined to bed	Number Analyzed	2080 participants	2129 participants
		0.4	0.4
Week 25: No problems	Number Analyzed	2062 participants	2081 participants
		83.8	82.7
Week 25: Some problems	Number Analyzed	2062 participants	2081 participants
		16.1	17.2
Week 25: Confined to bed	Number Analyzed	2062 participants	2081 participants
		0.1	0.1
EOT: No problems	Number Analyzed	2051 participants	2106 participants
		85.1	84.9
EOT: Some problems	Number Analyzed	2051 participants	2106 participants
		14.8	14.9
EOT: Confined to bed	Number Analyzed	2051 participants	2106 participants
		0.1	0.2
FU Month 18: No problems	Number Analyzed	1920 participants	1919 participants
		88.8	87.0
FU Month 18: Some problems	Number Analyzed	1920 participants	1919 participants
		11.2	12.8
FU Month 18: Confined to bed	Number Analyzed	1920 participants	1919 participants
		0.1	0.2
FU Month 24: No problems	Number Analyzed	1864 participants	1877 participants
		87.8	87.7
FU Month 24: Some problems	Number Analyzed	1864 participants	1877 participants
		12.1	12.1
FU Month 24: Confined to bed	Number Analyzed	1864 participants	1877 participants
		0.1	0.1
FU Month 36: No problems	Number Analyzed	1822 participants	1795 participants
		88.5	87.8
FU Month 36: Some problems	Number Analyzed	1822 participants	1795 participants
		11.5	12.1
FU Month 36: Confined to bed	Number Analyzed	1822 participants	1795 participants
		0.0	0.1

23. Secondary Outcome

Title	Percentage of Participants With Response for EQ-5D-3L Questionnaire: Self-Care Domain
Description	EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in self-care domain was reported: I have no problems with self-care; I have some problems washing or dressing myself; and I am unable to wash or dress myself. Response percentages may not add up to 100% due to data rounding.
Time Frame	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

Outcome Measure Data

Analysis Population Description

ITT population. Number analyzed=participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		2400	2404
Measure Type: Number; Unit of Measure: percentage of participants
Baseline: No problems	Number Analyzed	2289 participants	2310 participants
		89.7	90.7
Baseline: Some problems	Number Analyzed	2289 participants	2310 participants
		10.0	9.1
Baseline: Unable	Number Analyzed	2289 participants	2310 participants
		0.3	0.2
Week 13: No problems	Number Analyzed	2079 participants	2127 participants
		94.3	93.2
Week 13: Some problems	Number Analyzed	2079 participants	2127 participants
		5.3	6.4
Week 13: Unable	Number Analyzed	2079 participants	2127 participants
		0.4	0.4
Week 25: No problems	Number Analyzed	2057 participants	2077 participants
		95.5	95.0
Week 25: Some problems	Number Analyzed	2057 participants	2077 participants
		4.3	4.7
Week 25: Unable	Number Analyzed	2057 participants	2077 participants
		0.1	0.3
EOT: No problems	Number Analyzed	2051 participants	2106 participants
		95.4	95.8
EOT: Some problems	Number Analyzed	2051 participants	2106 participants
		4.4	4.0
EOT: Unable	Number Analyzed	2051 participants	2106 participants
		0.2	0.2
FU Month 18: No problems	Number Analyzed	1917 participants	1921 participants
		97.2	96.0
FU Month 18: Some problems	Number Analyzed	1917 participants	1921 participants
		2.6	3.6
FU Month 18: Unable	Number Analyzed	1917 participants	1921 participants
		0.2	0.3
FU Month 24: No problems	Number Analyzed	1861 participants	1877 participants
		96.9	96.3
FU Month 24: Some problems	Number Analyzed	1861 participants	1877 participants
		2.8	3.5
FU Month 24: Unable	Number Analyzed	1861 participants	1877 participants
		0.3	0.3
FU Month 36: No problems	Number Analyzed	1822 participants	1794 participants
		97.3	96.5
FU Month 36: Some problems	Number Analyzed	1822 participants	1794 participants
		2.5	3.2
FU Month 36: Unable	Number Analyzed	1822 participants	1794 participants
		0.2	0.3

24. Secondary Outcome

Title	Percentage of Participants With Response for EQ-5D-3L Questionnaire: Usual Activities Domain
Description	EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in usual activities domain was reported: I have no problems with performing my usual activities; I have some problems with performing my usual activities; and I am unable to perform my usual activities. Response percentages may not add up to 100% due to data rounding.
Time Frame	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

Outcome Measure Data

Analysis Population Description

ITT population. Number analyzed=participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		2400	2404
Measure Type: Number; Unit of Measure: percentage of participants
Baseline: No problems	Number Analyzed	2288 participants	2308 participants
		67.4	66.1
Baseline: Some problems	Number Analyzed	2288 participants	2308 participants
		30.4	32.2
Baseline: Unable	Number Analyzed	2288 participants	2308 participants
		2.2	1.7
Week 13: No problems	Number Analyzed	2078 participants	2128 participants
		56.8	54.1
Week 13: Some problems	Number Analyzed	2078 participants	2128 participants
		40.1	43.0
Week 13: Unable	Number Analyzed	2078 participants	2128 participants
		3.1	2.9
Week 25: No problems	Number Analyzed	2059 participants	2077 participants
		66.5	65.8
Week 25: Some problems	Number Analyzed	2059 participants	2077 participants
		32.2	32.7
Week 25: Unable	Number Analyzed	2059 participants	2077 participants
		1.2	1.4
EOT: No problems	Number Analyzed	2049 participants	2102 participants
		72.4	72.5
EOT: Some problems	Number Analyzed	2049 participants	2102 participants
		26.3	26.6
EOT: Unable	Number Analyzed	2049 participants	2102 participants
		1.3	0.9
FU Month 18: No problems	Number Analyzed	1919 participants	1918 participants
		78.5	76.3
FU Month 18: Some problems	Number Analyzed	1919 participants	1918 participants
		20.6	23.0
FU Month 18: Unable	Number Analyzed	1919 participants	1918 participants
		0.9	0.7
FU Month 24: No problems	Number Analyzed	1862 participants	1875 participants
		78.7	79.1
FU Month 24: Some problems	Number Analyzed	1862 participants	1875 participants
		20.4	19.7
FU Month 24: Unable	Number Analyzed	1862 participants	1875 participants
		0.9	1.1
FU Month 36: No problems	Number Analyzed	1821 participants	1794 participants
		80.9	79.8
FU Month 36: Some problems	Number Analyzed	1821 participants	1794 participants
		18.3	19.4
FU Month 36: Unable	Number Analyzed	1821 participants	1794 participants
		0.7	0.8

25. Secondary Outcome

Title	Percentage of Participants With Response for EQ-5D-3L Questionnaire: Pain/Discomfort Domain
Description	EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in pain/discomfort domain was reported: I have no pain or discomfort; I have moderate pain or discomfort; and I have extreme pain or discomfort. Response percentages may not add up to 100% due to data rounding.
Time Frame	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

Outcome Measure Data

Analysis Population Description

ITT population. Number analyzed=participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		2400	2404
Measure Type: Number; Unit of Measure: percentage of participants
Baseline: No pain/discomfort	Number Analyzed	2290 participants	2310 participants
		49.0	49.0
Baseline: Moderate pain/discomfort	Number Analyzed	2290 participants	2310 participants
		50.0	49.7
Baseline: Extreme pain/discomfort	Number Analyzed	2290 participants	2310 participants
		1.0	1.3
Week 13: No pain/discomfort	Number Analyzed	2076 participants	2127 participants
		44.6	40.5
Week 13: Moderate pain/discomfort	Number Analyzed	2076 participants	2127 participants
		52.7	56.5
Week 13: Extreme pain/discomfort	Number Analyzed	2076 participants	2127 participants
		2.7	3.0
Week 25: No pain/discomfort	Number Analyzed	2062 participants	2080 participants
		44.3	43.7
Week 25: Moderate pain/discomfort	Number Analyzed	2062 participants	2080 participants
		53.3	54.4
Week 25: Extreme pain/discomfort	Number Analyzed	2062 participants	2080 participants
		2.4	1.9
EOT: No pain/discomfort	Number Analyzed	2049 participants	2106 participants
		49.3	50.0
EOT: Moderate pain/discomfort	Number Analyzed	2049 participants	2106 participants
		48.5	47.6
EOT: Extreme pain/discomfort	Number Analyzed	2049 participants	2106 participants
		2.2	2.4
FU Month 18: No pain/discomfort	Number Analyzed	1918 participants	1918 participants
		51.3	53.1
FU Month 18: Moderate pain/discomfort	Number Analyzed	1918 participants	1918 participants
		46.6	44.7
FU Month 18: Extreme pain/discomfort	Number Analyzed	1918 participants	1918 participants
		2.1	2.1
FU Month 24: No pain/discomfort	Number Analyzed	1863 participants	1879 participants
		56.7	56.0
FU Month 24: Moderate pain/discomfort	Number Analyzed	1863 participants	1879 participants
		41.3	41.5
FU Month 24: Extreme pain/discomfort	Number Analyzed	1863 participants	1879 participants
		1.9	2.5
FU Month 36: No pain/discomfort	Number Analyzed	1823 participants	1793 participants
		59.5	57.8
FU Month 36: Moderate pain/discomfort	Number Analyzed	1823 participants	1793 participants
		38.9	40.1
FU Month 36: Extreme pain/discomfort	Number Analyzed	1823 participants	1793 participants
		1.6	2.1

26. Secondary Outcome

Title	Percentage of Participants With Response for EQ-5D-3L Questionnaire: Anxiety/Depression Domain
Description	EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in anxiety/depression domain was reported: I am not anxious or depressed; I am moderately anxious or depressed; and I am extremely anxious or depressed. Response percentages may not add up to 100% due to data rounding.
Time Frame	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

Outcome Measure Data

Analysis Population Description

ITT population. Number analyzed=participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		2400	2404
Measure Type: Number; Unit of Measure: percentage of participants
Baseline: Not anxious/depress	Number Analyzed	2286 participants	2310 participants
		47.1	44.7
Baseline: Moderate anxious/depress	Number Analyzed	2286 participants	2310 participants
		49.4	50.1
Baseline: Extreme anxious/depress	Number Analyzed	2286 participants	2310 participants
		3.5	5.2
Week 13: Not anxious/depress	Number Analyzed	2076 participants	2125 participants
		53.6	52.4
Week 13: Moderate anxious/depress	Number Analyzed	2076 participants	2125 participants
		43.4	44.0
Week 13: Extreme anxious/depress	Number Analyzed	2076 participants	2125 participants
		3.0	3.7
Week 25: No anxious/depress	Number Analyzed	2060 participants	2075 participants
		55.5	55.5
Week 25: Moderate anxious/depress	Number Analyzed	2060 participants	2075 participants
		41.9	41.8
Week 25: Extreme anxious/depress	Number Analyzed	2060 participants	2075 participants
		2.5	2.7
EOT: Not anxious/depress	Number Analyzed	2041 participants	2101 participants
		58.5	58.3
EOT: Moderate anxious/depress	Number Analyzed	2041 participants	2101 participants
		38.9	39.1
EOT: Extreme anxious/depress	Number Analyzed	2041 participants	2101 participants
		2.6	2.6
FU Month 18: Not anxious/depress	Number Analyzed	1916 participants	1915 participants
		61.4	59.9
FU Month 18: Moderate anxious/depress	Number Analyzed	1916 participants	1915 participants
		36.2	37.0
FU Month 18: Extreme anxious/depress	Number Analyzed	1916 participants	1915 participants
		2.4	3.1
FU Month 24: Not anxious/depress	Number Analyzed	1860 participants	1872 participants
		63.8	61.0
FU Month 24: Moderate anxious/depress	Number Analyzed	1860 participants	1872 participants
		33.8	36.2
FU Month 24: Extreme anxious/depress	Number Analyzed	1860 participants	1872 participants
		2.4	2.8
FU Month 36: Not anxious/depress	Number Analyzed	1815 participants	1787 participants
		64.0	61.6
FU Month 36: Moderate anxious/depress	Number Analyzed	1815 participants	1787 participants
		33.3	35.4
FU Month 36: Extreme anxious/depress	Number Analyzed	1815 participants	1787 participants
		2.6	3.0

27. Secondary Outcome

Title	Trough Serum Concentration (Cmin) of Pertuzumab
Description	[Not Specified]
Time Frame	Cycles 1, 10 and 15 (Cycle length=21 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) evaluable participants were defined as those who received at least one active pertuzumab and/or trastuzumab treatment and had at least one PK sample collected. Number analyzed=participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).
Overall Number of Participants Analyzed		36
Mean (Standard Deviation); Unit of Measure: micrograms per milliliter (mcg/mL)
Cycle 1	Number Analyzed	31 participants
		68.0 (16.6)
Cycle 10	Number Analyzed	31 participants
		88.1 (34.4)
Cycle 15	Number Analyzed	27 participants
		95.5 (51.5)

28. Secondary Outcome

Title	Cmin of Trastuzumab
Description	[Not Specified]
Time Frame	Cycles 1, 10 and 15 (Cycle length=21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable participants. Number analyzed=participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		36	34
Mean (Standard Deviation); Unit of Measure: mcg/mL
Cycle 1	Number Analyzed	32 participants	31 participants
		32.1 (13.4)	34.1 (11.4)
Cycle 10	Number Analyzed	33 participants	26 participants
		65.0 (39.6)	68.4 (23.0)
Cycle 15	Number Analyzed	27 participants	22 participants
		72.9 (46.1)	71.0 (30.4)

29. Secondary Outcome

Title	Peak Serum Concentration (Cmax) of Pertuzumab
Description	[Not Specified]
Time Frame	Cycles 1, 10 and 15 (Cycle length=21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable participants. Number analyzed=participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).
Overall Number of Participants Analyzed		36
Mean (Standard Deviation); Unit of Measure: mcg/mL
Cycle 1	Number Analyzed	33 participants
		237 (118)
Cycle 10	Number Analyzed	29 participants
		222 (92.2)
Cycle 15	Number Analyzed	24 participants
		206 (94.9)

30. Secondary Outcome

Title	Cmax of Trastuzumab
Description	[Not Specified]
Time Frame	Cycles 1, 10 and 15 (Cycle length=21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable participants. Number analyzed=participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title		Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description:		Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
Overall Number of Participants Analyzed		36	34
Mean (Standard Deviation); Unit of Measure: mcg/mL
Cycle 1	Number Analyzed	36 participants	33 participants
		180 (81.0)	190 (51.6)
Cycle 10	Number Analyzed	33 participants	27 participants
		219 (94.6)	225 (70.7)
Cycle 15	Number Analyzed	25 participants	21 participants
		187 (95.1)	234 (73.5)

Adverse Events

Time Frame	Randomization until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)
Adverse Event Reporting Description	Safety population. 38 participants randomized to pertuzumab arm received study treatment but did not receive pertuzumab and were included in the placebo arm for safety analyses. 24 participants randomized to placebo arm received at least 1 dose of pertuzumab and were included in pertuzumab arm for safety analyses.
Arm/Group Title	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
Arm/Group Description	Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
All-Cause Mortality
	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	692/2364 (29.27%)	585/2405 (24.32%)
Blood and lymphatic system disorders
Agranulocytosis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Anaemia * 1	10/2364 (0.42%)	8/2405 (0.33%)
Bone marrow failure * 1	2/2364 (0.08%)	3/2405 (0.12%)
Cytopenia * 1	0/2364 (0.00%)	1/2405 (0.04%)
Febrile bone marrow aplasia * 1	9/2364 (0.38%)	7/2405 (0.29%)
Febrile neutropenia * 1	208/2364 (8.80%)	196/2405 (8.15%)
Haemolytic anaemia * 1	1/2364 (0.04%)	0/2405 (0.00%)
Histiocytosis haematophagic * 1	1/2364 (0.04%)	0/2405 (0.00%)
Leukopenia * 1	3/2364 (0.13%)	5/2405 (0.21%)
Lymphadenopathy * 1	1/2364 (0.04%)	1/2405 (0.04%)
Microangiopathic haemolytic anaemia * 1	0/2364 (0.00%)	1/2405 (0.04%)
Neutropenia * 1	26/2364 (1.10%)	32/2405 (1.33%)
Pancytopenia * 1	1/2364 (0.04%)	1/2405 (0.04%)
Thrombocytopenia * 1	2/2364 (0.08%)	4/2405 (0.17%)
Cardiac disorders
Acute coronary syndrome * 1	0/2364 (0.00%)	1/2405 (0.04%)
Acute myocardial infarction * 1	0/2364 (0.00%)	1/2405 (0.04%)
Angina pectoris * 1	0/2364 (0.00%)	1/2405 (0.04%)
Arrhythmia * 1	1/2364 (0.04%)	1/2405 (0.04%)
Atrial fibrillation * 1	3/2364 (0.13%)	2/2405 (0.08%)
Atrial thrombosis * 1	1/2364 (0.04%)	1/2405 (0.04%)
Bradycardia * 1	0/2364 (0.00%)	1/2405 (0.04%)
Cardiac arrest * 1	0/2364 (0.00%)	1/2405 (0.04%)
Cardiac failure * 1	33/2364 (1.40%)	17/2405 (0.71%)
Cardiac failure congestive * 1	1/2364 (0.04%)	1/2405 (0.04%)
Coronary artery stenosis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Extrasystoles * 1	1/2364 (0.04%)	0/2405 (0.00%)
Metabolic cardiomyopathy * 1	0/2364 (0.00%)	1/2405 (0.04%)
Myocardial infarction * 1	4/2364 (0.17%)	2/2405 (0.08%)
Palpitations * 1	1/2364 (0.04%)	0/2405 (0.00%)
Pericardial effusion * 1	2/2364 (0.08%)	1/2405 (0.04%)
Sinus node dysfunction * 1	0/2364 (0.00%)	1/2405 (0.04%)
Stress cardiomyopathy * 1	0/2364 (0.00%)	1/2405 (0.04%)
Tachycardia * 1	1/2364 (0.04%)	0/2405 (0.00%)
Tachycardia paroxysmal * 1	0/2364 (0.00%)	1/2405 (0.04%)
Ventricular arrhythmia * 1	0/2364 (0.00%)	1/2405 (0.04%)
Ventricular fibrillation * 1	1/2364 (0.04%)	0/2405 (0.00%)
Congenital, familial and genetic disorders
Aplasia * 1	0/2364 (0.00%)	1/2405 (0.04%)
Pyloric stenosis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Ear and labyrinth disorders
External ear inflammation * 1	0/2364 (0.00%)	1/2405 (0.04%)
Sudden hearing loss * 1	1/2364 (0.04%)	0/2405 (0.00%)
Tympanic membrane perforation * 1	0/2364 (0.00%)	1/2405 (0.04%)
Vertigo * 1	5/2364 (0.21%)	4/2405 (0.17%)
Vestibular disorder * 1	1/2364 (0.04%)	0/2405 (0.00%)
Endocrine disorders
Goitre * 1	1/2364 (0.04%)	0/2405 (0.00%)
Hyperthyroidism * 1	0/2364 (0.00%)	1/2405 (0.04%)
Inappropriate antidiuretic hormone secretion * 1	0/2364 (0.00%)	1/2405 (0.04%)
Thyroid disorder * 1	1/2364 (0.04%)	0/2405 (0.00%)
Eye disorders
Optic nerve disorder * 1	1/2364 (0.04%)	0/2405 (0.00%)
Papilloedema * 1	1/2364 (0.04%)	0/2405 (0.00%)
Visual acuity reduced * 1	0/2364 (0.00%)	1/2405 (0.04%)
Gastrointestinal disorders
Abdominal pain * 1	6/2364 (0.25%)	7/2405 (0.29%)
Abdominal pain upper * 1	4/2364 (0.17%)	3/2405 (0.12%)
Anal haemorrhage * 1	1/2364 (0.04%)	0/2405 (0.00%)
Colitis * 1	2/2364 (0.08%)	5/2405 (0.21%)
Constipation * 1	4/2364 (0.17%)	2/2405 (0.08%)
Diarrhoea * 1	58/2364 (2.45%)	18/2405 (0.75%)
Diverticular perforation * 1	0/2364 (0.00%)	1/2405 (0.04%)
Diverticulum intestinal haemorrhagic * 1	0/2364 (0.00%)	1/2405 (0.04%)
Duodenal perforation * 1	0/2364 (0.00%)	1/2405 (0.04%)
Duodenal ulcer * 1	1/2364 (0.04%)	0/2405 (0.00%)
Duodenal ulcer haemorrhage * 1	0/2364 (0.00%)	1/2405 (0.04%)
Duodenal ulcer perforation * 1	0/2364 (0.00%)	1/2405 (0.04%)
Enteritis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Enterocolitis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Femoral hernia strangulated * 1	0/2364 (0.00%)	1/2405 (0.04%)
Gastric ulcer * 1	1/2364 (0.04%)	1/2405 (0.04%)
Gastric ulcer haemorrhage * 1	2/2364 (0.08%)	0/2405 (0.00%)
Gastritis * 1	1/2364 (0.04%)	1/2405 (0.04%)
Gastrointestinal disorder * 1	1/2364 (0.04%)	0/2405 (0.00%)
Gastrointestinal haemorrhage * 1	1/2364 (0.04%)	0/2405 (0.00%)
Gastrointestinal pain * 1	1/2364 (0.04%)	0/2405 (0.00%)
Gastrointestinal perforation * 1	0/2364 (0.00%)	1/2405 (0.04%)
Gastrointestinal toxicity * 1	1/2364 (0.04%)	0/2405 (0.00%)
Gastrooesophageal reflux disease * 1	1/2364 (0.04%)	1/2405 (0.04%)
Haemorrhoidal haemorrhage * 1	0/2364 (0.00%)	1/2405 (0.04%)
Haemorrhoids * 1	2/2364 (0.08%)	1/2405 (0.04%)
Ileus * 1	1/2364 (0.04%)	1/2405 (0.04%)
Inguinal hernia * 1	1/2364 (0.04%)	0/2405 (0.00%)
Intestinal haemorrhage * 1	1/2364 (0.04%)	0/2405 (0.00%)
Intestinal ischaemia * 1	0/2364 (0.00%)	1/2405 (0.04%)
Intestinal obstruction * 1	1/2364 (0.04%)	1/2405 (0.04%)
Intra-abdominal haematoma * 1	1/2364 (0.04%)	0/2405 (0.00%)
Intussusception * 1	0/2364 (0.00%)	1/2405 (0.04%)
Lower gastrointestinal haemorrhage * 1	1/2364 (0.04%)	0/2405 (0.00%)
Nausea * 1	18/2364 (0.76%)	14/2405 (0.58%)
Neutropenic colitis * 1	0/2364 (0.00%)	1/2405 (0.04%)
Oedema mouth * 1	1/2364 (0.04%)	0/2405 (0.00%)
Oesophageal pain * 1	1/2364 (0.04%)	1/2405 (0.04%)
Oral pain * 1	0/2364 (0.00%)	1/2405 (0.04%)
Pancreatitis * 1	1/2364 (0.04%)	3/2405 (0.12%)
Pancreatitis acute * 1	2/2364 (0.08%)	0/2405 (0.00%)
Proctitis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Rectal haemorrhage * 1	4/2364 (0.17%)	1/2405 (0.04%)
Small intestinal haemorrhage * 1	0/2364 (0.00%)	1/2405 (0.04%)
Small intestinal obstruction * 1	1/2364 (0.04%)	0/2405 (0.00%)
Stomatitis * 1	7/2364 (0.30%)	1/2405 (0.04%)
Subileus * 1	0/2364 (0.00%)	1/2405 (0.04%)
Toothache * 1	0/2364 (0.00%)	1/2405 (0.04%)
Upper gastrointestinal haemorrhage * 1	1/2364 (0.04%)	2/2405 (0.08%)
Vomiting * 1	19/2364 (0.80%)	15/2405 (0.62%)
General disorders
Asthenia * 1	2/2364 (0.08%)	1/2405 (0.04%)
Chest pain * 1	4/2364 (0.17%)	6/2405 (0.25%)
Chills * 1	2/2364 (0.08%)	0/2405 (0.00%)
Cyst * 1	1/2364 (0.04%)	0/2405 (0.00%)
Device related thrombosis * 1	1/2364 (0.04%)	3/2405 (0.12%)
Fatigue * 1	7/2364 (0.30%)	5/2405 (0.21%)
General physical health deterioration * 1	5/2364 (0.21%)	5/2405 (0.21%)
Generalised oedema * 1	1/2364 (0.04%)	0/2405 (0.00%)
Influenza like illness * 1	2/2364 (0.08%)	1/2405 (0.04%)
Malaise * 1	3/2364 (0.13%)	2/2405 (0.08%)
Mass * 1	1/2364 (0.04%)	0/2405 (0.00%)
Mucosal inflammation * 1	4/2364 (0.17%)	1/2405 (0.04%)
Non-cardiac chest pain * 1	0/2364 (0.00%)	1/2405 (0.04%)
Oedema peripheral * 1	0/2364 (0.00%)	1/2405 (0.04%)
Pyrexia * 1	39/2364 (1.65%)	45/2405 (1.87%)
Hepatobiliary disorders
Biliary colic * 1	1/2364 (0.04%)	0/2405 (0.00%)
Cholangitis * 1	0/2364 (0.00%)	1/2405 (0.04%)
Cholecystitis * 1	0/2364 (0.00%)	1/2405 (0.04%)
Cholecystitis acute * 1	1/2364 (0.04%)	0/2405 (0.00%)
Cholelithiasis * 1	1/2364 (0.04%)	1/2405 (0.04%)
Drug-induced liver injury * 1	1/2364 (0.04%)	0/2405 (0.00%)
Hepatic failure * 1	1/2364 (0.04%)	0/2405 (0.00%)
Hepatic function abnormal * 1	2/2364 (0.08%)	0/2405 (0.00%)
Immune system disorders
Anaphylactic reaction * 1	1/2364 (0.04%)	3/2405 (0.12%)
Anaphylactic shock * 1	0/2364 (0.00%)	2/2405 (0.08%)
Drug hypersensitivity * 1	3/2364 (0.13%)	0/2405 (0.00%)
Hypersensitivity * 1	11/2364 (0.47%)	3/2405 (0.12%)
Infections and infestations
Abdominal abscess * 1	0/2364 (0.00%)	1/2405 (0.04%)
Abdominal infection * 1	0/2364 (0.00%)	1/2405 (0.04%)
Abscess * 1	1/2364 (0.04%)	1/2405 (0.04%)
Abscess limb * 1	0/2364 (0.00%)	2/2405 (0.08%)
Abscess oral * 1	1/2364 (0.04%)	0/2405 (0.00%)
Acute hepatitis B * 1	0/2364 (0.00%)	1/2405 (0.04%)
Anal abscess * 1	1/2364 (0.04%)	0/2405 (0.00%)
Anorectal infection * 1	1/2364 (0.04%)	0/2405 (0.00%)
Appendicitis * 1	1/2364 (0.04%)	2/2405 (0.08%)
Appendicitis perforated * 1	1/2364 (0.04%)	0/2405 (0.00%)
Bacteraemia * 1	3/2364 (0.13%)	1/2405 (0.04%)
Bacterial infection * 1	2/2364 (0.08%)	0/2405 (0.00%)
Breast abscess * 1	1/2364 (0.04%)	1/2405 (0.04%)
Breast cellulitis * 1	1/2364 (0.04%)	1/2405 (0.04%)
Bronchitis * 1	7/2364 (0.30%)	3/2405 (0.12%)
Cellulitis * 1	14/2364 (0.59%)	12/2405 (0.50%)
Chronic sinusitis * 1	0/2364 (0.00%)	1/2405 (0.04%)
Clostridium colitis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Clostridium difficile colitis * 1	2/2364 (0.08%)	0/2405 (0.00%)
Clostridium difficile infection * 1	1/2364 (0.04%)	0/2405 (0.00%)
Device related infection * 1	7/2364 (0.30%)	9/2405 (0.37%)
Device related sepsis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Diarrhoea infectious * 1	1/2364 (0.04%)	1/2405 (0.04%)
Disseminated tuberculosis * 1	0/2364 (0.00%)	1/2405 (0.04%)
Diverticulitis * 1	3/2364 (0.13%)	6/2405 (0.25%)
Erysipelas * 1	3/2364 (0.13%)	2/2405 (0.08%)
Escherichia infection * 1	1/2364 (0.04%)	0/2405 (0.00%)
Gastroenteritis * 1	8/2364 (0.34%)	3/2405 (0.12%)
Gastroenteritis viral * 1	1/2364 (0.04%)	0/2405 (0.00%)
H1N1 influenza * 1	0/2364 (0.00%)	1/2405 (0.04%)
Hepatitis B * 1	1/2364 (0.04%)	0/2405 (0.00%)
Herpes zoster * 1	1/2364 (0.04%)	0/2405 (0.00%)
Herpes zoster disseminated * 1	0/2364 (0.00%)	1/2405 (0.04%)
Infected lymphocele * 1	0/2364 (0.00%)	1/2405 (0.04%)
Infected seroma * 1	0/2364 (0.00%)	2/2405 (0.08%)
Infection * 1	7/2364 (0.30%)	6/2405 (0.25%)
Influenza * 1	1/2364 (0.04%)	0/2405 (0.00%)
Laryngitis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Localised infection * 1	0/2364 (0.00%)	1/2405 (0.04%)
Lower respiratory tract infection * 1	4/2364 (0.17%)	3/2405 (0.12%)
Lung infection * 1	3/2364 (0.13%)	4/2405 (0.17%)
Mastitis * 1	4/2364 (0.17%)	4/2405 (0.17%)
Nasopharyngitis * 1	3/2364 (0.13%)	0/2405 (0.00%)
Neutropenic infection * 1	0/2364 (0.00%)	1/2405 (0.04%)
Neutropenic sepsis * 1	10/2364 (0.42%)	4/2405 (0.17%)
Oral candidiasis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Otitis media acute * 1	1/2364 (0.04%)	0/2405 (0.00%)
Paronychia * 1	1/2364 (0.04%)	0/2405 (0.00%)
Periodontitis * 1	0/2364 (0.00%)	1/2405 (0.04%)
Peritonsillar abscess * 1	1/2364 (0.04%)	0/2405 (0.00%)
Pharyngitis * 1	2/2364 (0.08%)	0/2405 (0.00%)
Phlebitis infective * 1	1/2364 (0.04%)	0/2405 (0.00%)
Pleural infection * 1	1/2364 (0.04%)	0/2405 (0.00%)
Pneumococcal infection * 1	1/2364 (0.04%)	0/2405 (0.00%)
Pneumocystis jirovecii pneumonia * 1	1/2364 (0.04%)	0/2405 (0.00%)
Pneumonia * 1	16/2364 (0.68%)	23/2405 (0.96%)
Pneumonia bacterial * 1	0/2364 (0.00%)	1/2405 (0.04%)
Pneumonia pseudomonal * 1	1/2364 (0.04%)	0/2405 (0.00%)
Pneumonia streptococcal * 1	0/2364 (0.00%)	1/2405 (0.04%)
Postoperative wound infection * 1	1/2364 (0.04%)	0/2405 (0.00%)
Pseudomonal bacteraemia * 1	0/2364 (0.00%)	1/2405 (0.04%)
Pyelonephritis * 1	0/2364 (0.00%)	2/2405 (0.08%)
Pyelonephritis acute * 1	0/2364 (0.00%)	2/2405 (0.08%)
Rectal abscess * 1	0/2364 (0.00%)	1/2405 (0.04%)
Respiratory tract infection * 1	2/2364 (0.08%)	2/2405 (0.08%)
Salpingo-oophoritis * 1	0/2364 (0.00%)	1/2405 (0.04%)
Sepsis * 1	7/2364 (0.30%)	9/2405 (0.37%)
Septic shock * 1	0/2364 (0.00%)	2/2405 (0.08%)
Serratia infection * 1	0/2364 (0.00%)	1/2405 (0.04%)
Sinusitis * 1	2/2364 (0.08%)	0/2405 (0.00%)
Skin infection * 1	2/2364 (0.08%)	5/2405 (0.21%)
Soft tissue infection * 1	3/2364 (0.13%)	0/2405 (0.00%)
Staphylococcal bacteraemia * 1	0/2364 (0.00%)	1/2405 (0.04%)
Staphylococcal infection * 1	1/2364 (0.04%)	0/2405 (0.00%)
Staphylococcal sepsis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Staphylococcal skin infection * 1	1/2364 (0.04%)	0/2405 (0.00%)
Streptococcal sepsis * 1	0/2364 (0.00%)	1/2405 (0.04%)
Subcutaneous abscess * 1	1/2364 (0.04%)	2/2405 (0.08%)
Tonsillitis * 1	1/2364 (0.04%)	1/2405 (0.04%)
Tooth infection * 1	0/2364 (0.00%)	1/2405 (0.04%)
Upper respiratory tract infection * 1	9/2364 (0.38%)	8/2405 (0.33%)
Urinary tract infection * 1	8/2364 (0.34%)	9/2405 (0.37%)
Urosepsis * 1	2/2364 (0.08%)	1/2405 (0.04%)
Varicella * 1	0/2364 (0.00%)	1/2405 (0.04%)
Viral Infection * 1	2/2364 (0.08%)	1/2405 (0.04%)
Viral upper respiratory tract infection * 1	1/2364 (0.04%)	0/2405 (0.00%)
Vulval abscess * 1	1/2364 (0.04%)	0/2405 (0.00%)
Wound infection * 1	5/2364 (0.21%)	2/2405 (0.08%)
Lymphangitis * 1	2/2364 (0.08%)	0/2405 (0.00%)
Injury, poisoning and procedural complications
Accidental overdose * 1	1/2364 (0.04%)	0/2405 (0.00%)
Ankle fracture * 1	0/2364 (0.00%)	1/2405 (0.04%)
Avulsion fracture * 1	0/2364 (0.00%)	1/2405 (0.04%)
Concussion * 1	1/2364 (0.04%)	0/2405 (0.00%)
Fall * 1	1/2364 (0.04%)	0/2405 (0.00%)
Femoral neck fracture * 1	1/2364 (0.04%)	1/2405 (0.04%)
Fractured sacrum * 1	0/2364 (0.00%)	1/2405 (0.04%)
Graft thrombosis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Humerus fracture * 1	5/2364 (0.21%)	1/2405 (0.04%)
Ilium fracture * 1	1/2364 (0.04%)	0/2405 (0.00%)
Infusion related reaction * 1	3/2364 (0.13%)	1/2405 (0.04%)
Intentional overdose * 1	0/2364 (0.00%)	1/2405 (0.04%)
Joint dislocation * 1	0/2364 (0.00%)	1/2405 (0.04%)
Laceration * 1	1/2364 (0.04%)	0/2405 (0.00%)
Lower limb fracture * 1	0/2364 (0.00%)	1/2405 (0.04%)
Multiple fractures * 1	1/2364 (0.04%)	0/2405 (0.00%)
Pneumoconiosis * 1	0/2364 (0.00%)	1/2405 (0.04%)
Pneumothorax traumatic * 1	0/2364 (0.00%)	1/2405 (0.04%)
Post procedural haematoma * 1	0/2364 (0.00%)	1/2405 (0.04%)
Post procedural haemorrhage * 1	1/2364 (0.04%)	0/2405 (0.00%)
Postoperative wound complication * 1	1/2364 (0.04%)	0/2405 (0.00%)
Procedural complication * 1	1/2364 (0.04%)	0/2405 (0.00%)
Procedural pain * 1	0/2364 (0.00%)	1/2405 (0.04%)
Pulmonary radiation injury * 1	0/2364 (0.00%)	1/2405 (0.04%)
Radiation skin injury * 1	1/2364 (0.04%)	0/2405 (0.00%)
Radius fracture * 1	3/2364 (0.13%)	0/2405 (0.00%)
Road traffic accident * 1	1/2364 (0.04%)	0/2405 (0.00%)
Seroma * 1	0/2364 (0.00%)	3/2405 (0.12%)
Spinal compression fracture * 1	1/2364 (0.04%)	0/2405 (0.00%)
Subarachnoid haemorrhage * 1	3/2364 (0.13%)	0/2405 (0.00%)
Thermal burn * 1	0/2364 (0.00%)	1/2405 (0.04%)
Tibia fracture * 1	2/2364 (0.08%)	0/2405 (0.00%)
Toxicity to various agents * 1	0/2364 (0.00%)	1/2405 (0.04%)
Upper limb fracture * 1	1/2364 (0.04%)	0/2405 (0.00%)
Wound dehiscence * 1	2/2364 (0.08%)	1/2405 (0.04%)
Wrist fracture * 1	1/2364 (0.04%)	0/2405 (0.00%)
Investigations
Alanine aminotransferase increased * 1	1/2364 (0.04%)	2/2405 (0.08%)
Aspartate aminotransferase increased * 1	0/2364 (0.00%)	1/2405 (0.04%)
Blood creatinine increased * 1	1/2364 (0.04%)	1/2405 (0.04%)
Blood glucose fluctuation * 1	0/2364 (0.00%)	1/2405 (0.04%)
Body temperature increased * 1	0/2364 (0.00%)	1/2405 (0.04%)
Ejection fraction decreased * 1	11/2364 (0.47%)	7/2405 (0.29%)
Haemoglobin decreased * 1	0/2364 (0.00%)	1/2405 (0.04%)
Liver function test increased * 1	1/2364 (0.04%)	0/2405 (0.00%)
Neutrophil count decreased * 1	7/2364 (0.30%)	3/2405 (0.12%)
Troponin increased * 1	2/2364 (0.08%)	0/2405 (0.00%)
Weight decreased * 1	1/2364 (0.04%)	0/2405 (0.00%)
White blood cell count decreased * 1	2/2364 (0.08%)	0/2405 (0.00%)
Platelet count decreased * 1	1/2364 (0.04%)	1/2405 (0.04%)
Metabolism and nutrition disorders
Decreased appetite * 1	6/2364 (0.25%)	0/2405 (0.00%)
Dehydration * 1	18/2364 (0.76%)	5/2405 (0.21%)
Diabetes mellitus * 1	0/2364 (0.00%)	1/2405 (0.04%)
Electrolyte imbalance * 1	1/2364 (0.04%)	1/2405 (0.04%)
Fluid retention * 1	0/2364 (0.00%)	1/2405 (0.04%)
Hyperglycaemia * 1	1/2364 (0.04%)	2/2405 (0.08%)
Hyperkalaemia * 1	1/2364 (0.04%)	0/2405 (0.00%)
Hypocalcaemia * 1	1/2364 (0.04%)	0/2405 (0.00%)
Hypoglycaemia * 1	2/2364 (0.08%)	0/2405 (0.00%)
Hypokalaemia * 1	8/2364 (0.34%)	2/2405 (0.08%)
Hypomagnesaemia * 1	5/2364 (0.21%)	1/2405 (0.04%)
Hyponatraemia * 1	1/2364 (0.04%)	1/2405 (0.04%)
Hypophosphataemia * 1	1/2364 (0.04%)	0/2405 (0.00%)
Hypovolaemia * 1	1/2364 (0.04%)	1/2405 (0.04%)
Tumour lysis syndrome * 1	0/2364 (0.00%)	1/2405 (0.04%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	0/2364 (0.00%)	1/2405 (0.04%)
Back pain * 1	0/2364 (0.00%)	2/2405 (0.08%)
Intervertebral disc protrusion * 1	2/2364 (0.08%)	1/2405 (0.04%)
Musculoskeletal chest pain * 1	1/2364 (0.04%)	0/2405 (0.00%)
Musculoskeletal pain * 1	0/2364 (0.00%)	1/2405 (0.04%)
Myalgia * 1	2/2364 (0.08%)	3/2405 (0.12%)
Osteonecrosis of jaw * 1	1/2364 (0.04%)	0/2405 (0.00%)
Pain in extremity * 1	2/2364 (0.08%)	0/2405 (0.00%)
Rotator cuff syndrome * 1	1/2364 (0.04%)	0/2405 (0.00%)
Sjogren's syndrome * 1	0/2364 (0.00%)	1/2405 (0.04%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia * 1	1/2364 (0.04%)	1/2405 (0.04%)
Adenocarcinoma pancreas * 1	0/2364 (0.00%)	1/2405 (0.04%)
Basal cell carcinoma * 1	1/2364 (0.04%)	3/2405 (0.12%)
Benign breast neoplasm * 1	0/2364 (0.00%)	1/2405 (0.04%)
Gastric cancer * 1	1/2364 (0.04%)	0/2405 (0.00%)
Gastric neoplasm * 1	0/2364 (0.00%)	1/2405 (0.04%)
Intraductal proliferative breast lesion * 1	1/2364 (0.04%)	0/2405 (0.00%)
Lentigo maligna * 1	0/2364 (0.00%)	1/2405 (0.04%)
Lung neoplasm malignant * 1	1/2364 (0.04%)	0/2405 (0.00%)
Malignant melanoma * 1	0/2364 (0.00%)	2/2405 (0.08%)
Malignant melanoma in situ * 1	1/2364 (0.04%)	0/2405 (0.00%)
Meningioma * 1	1/2364 (0.04%)	0/2405 (0.00%)
Monoclonal gammopathy * 1	1/2364 (0.04%)	0/2405 (0.00%)
Myelodysplastic syndrome * 1	0/2364 (0.00%)	1/2405 (0.04%)
Neurilemmoma benign * 1	0/2364 (0.00%)	1/2405 (0.04%)
Non-small cell lung cancer metastatic * 1	1/2364 (0.04%)	0/2405 (0.00%)
Pancreatic carcinoma * 1	1/2364 (0.04%)	0/2405 (0.00%)
Papillary thyroid cancer * 1	0/2364 (0.00%)	1/2405 (0.04%)
Parathyroid tumour benign * 1	0/2364 (0.00%)	1/2405 (0.04%)
Pelvic neoplasm * 1	0/2364 (0.00%)	1/2405 (0.04%)
Small cell lung cancer * 1	0/2364 (0.00%)	1/2405 (0.04%)
Squamous cell carcinoma * 1	0/2364 (0.00%)	2/2405 (0.08%)
Transitional cell carcinoma * 1	1/2364 (0.04%)	0/2405 (0.00%)
Uterine leiomyoma * 1	1/2364 (0.04%)	1/2405 (0.04%)
Nervous system disorders
Ataxia * 1	1/2364 (0.04%)	0/2405 (0.00%)
Autonomic nervous system imbalance * 1	1/2364 (0.04%)	0/2405 (0.00%)
Cerebral haemorrhage * 1	3/2364 (0.13%)	0/2405 (0.00%)
Cerebral infarction * 1	0/2364 (0.00%)	1/2405 (0.04%)
Cerebrovascular accident * 1	1/2364 (0.04%)	1/2405 (0.04%)
Dizziness * 1	1/2364 (0.04%)	2/2405 (0.08%)
Facial neuralgia * 1	0/2364 (0.00%)	1/2405 (0.04%)
Haemorrhage intracranial * 1	0/2364 (0.00%)	1/2405 (0.04%)
Head titubation * 1	1/2364 (0.04%)	0/2405 (0.00%)
Headache * 1	0/2364 (0.00%)	2/2405 (0.08%)
Intercostal neuralgia * 1	0/2364 (0.00%)	1/2405 (0.04%)
Intracranial aneurysm * 1	1/2364 (0.04%)	1/2405 (0.04%)
Lacunar infarction * 1	0/2364 (0.00%)	1/2405 (0.04%)
Loss of consciousness * 1	1/2364 (0.04%)	1/2405 (0.04%)
Migraine with aura * 1	1/2364 (0.04%)	0/2405 (0.00%)
Neuropathy peripheral * 1	1/2364 (0.04%)	0/2405 (0.00%)
Neurotoxicity * 1	0/2364 (0.00%)	1/2405 (0.04%)
Paraesthesia * 1	2/2364 (0.08%)	1/2405 (0.04%)
Peripheral sensory neuropathy * 1	1/2364 (0.04%)	0/2405 (0.00%)
Sciatica * 1	1/2364 (0.04%)	0/2405 (0.00%)
Seizure * 1	3/2364 (0.13%)	1/2405 (0.04%)
Sunct syndrome * 1	1/2364 (0.04%)	0/2405 (0.00%)
Syncope * 1	13/2364 (0.55%)	5/2405 (0.21%)
Thalamic infarction * 1	0/2364 (0.00%)	1/2405 (0.04%)
Transient ischaemic attack * 1	1/2364 (0.04%)	1/2405 (0.04%)
Visual field defect * 1	0/2364 (0.00%)	1/2405 (0.04%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous * 1	0/2364 (0.00%)	1/2405 (0.04%)
Product Issues
Device breakage * 1	0/2364 (0.00%)	1/2405 (0.04%)
Device dislocation * 1	1/2364 (0.04%)	0/2405 (0.00%)
Device extrusion * 1	1/2364 (0.04%)	0/2405 (0.00%)
Psychiatric disorders
Anxiety * 1	0/2364 (0.00%)	1/2405 (0.04%)
Delusional disorder, unspecified type * 1	0/2364 (0.00%)	1/2405 (0.04%)
Depression * 1	5/2364 (0.21%)	3/2405 (0.12%)
Hypomania * 1	1/2364 (0.04%)	0/2405 (0.00%)
Major depression * 1	1/2364 (0.04%)	0/2405 (0.00%)
Mania * 1	0/2364 (0.00%)	1/2405 (0.04%)
Mental disorder * 1	2/2364 (0.08%)	0/2405 (0.00%)
Persistent depressive disorder * 1	0/2364 (0.00%)	1/2405 (0.04%)
Personality change * 1	0/2364 (0.00%)	1/2405 (0.04%)
Psychogenic seizure * 1	1/2364 (0.04%)	0/2405 (0.00%)
Psychotic disorder * 1	1/2364 (0.04%)	1/2405 (0.04%)
Reactive psychosis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Suicidal ideation * 1	0/2364 (0.00%)	1/2405 (0.04%)
Suicide attempt * 1	3/2364 (0.13%)	2/2405 (0.08%)
Renal and urinary disorders
Acute kidney injury * 1	5/2364 (0.21%)	2/2405 (0.08%)
Dysuria * 1	0/2364 (0.00%)	1/2405 (0.04%)
Renal colic * 1	0/2364 (0.00%)	1/2405 (0.04%)
Renal failure * 1	1/2364 (0.04%)	1/2405 (0.04%)
Renal impairment * 1	0/2364 (0.00%)	1/2405 (0.04%)
Ureteric obstruction * 1	0/2364 (0.00%)	1/2405 (0.04%)
Ureterolithiasis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Urinary incontinence * 1	1/2364 (0.04%)	0/2405 (0.00%)
Urinary retention * 1	1/2364 (0.04%)	1/2405 (0.04%)
Reproductive system and breast disorders
Breast inflammation * 1	0/2364 (0.00%)	2/2405 (0.08%)
Breast pain * 1	1/2364 (0.04%)	1/2405 (0.04%)
Cervical polyp * 1	1/2364 (0.04%)	0/2405 (0.00%)
Menorrhagia * 1	1/2364 (0.04%)	0/2405 (0.00%)
Ovarian cyst * 1	1/2364 (0.04%)	1/2405 (0.04%)
Pelvic cyst * 1	0/2364 (0.00%)	1/2405 (0.04%)
Uterine haemorrhage * 1	1/2364 (0.04%)	0/2405 (0.00%)
Vaginal haemorrhage * 1	1/2364 (0.04%)	0/2405 (0.00%)
Respiratory, thoracic and mediastinal disorders
Asthma * 1	1/2364 (0.04%)	2/2405 (0.08%)
Atelectasis * 1	1/2364 (0.04%)	0/2405 (0.00%)
Bronchiectasis * 1	0/2364 (0.00%)	1/2405 (0.04%)
Bronchospasm * 1	1/2364 (0.04%)	0/2405 (0.00%)
Cough * 1	2/2364 (0.08%)	2/2405 (0.08%)
Dysphonia * 1	1/2364 (0.04%)	0/2405 (0.00%)
Dyspnoea * 1	6/2364 (0.25%)	7/2405 (0.29%)
Dyspnoea exertional * 1	0/2364 (0.00%)	1/2405 (0.04%)
Epistaxis * 1	3/2364 (0.13%)	1/2405 (0.04%)
Interstitial lung disease * 1	1/2364 (0.04%)	2/2405 (0.08%)
Lung consolidation * 1	1/2364 (0.04%)	0/2405 (0.00%)
Lung infiltration * 1	0/2364 (0.00%)	1/2405 (0.04%)
Nasal oedema * 1	1/2364 (0.04%)	0/2405 (0.00%)
Nasal polyps * 1	0/2364 (0.00%)	1/2405 (0.04%)
Oropharyngeal discomfort * 1	0/2364 (0.00%)	1/2405 (0.04%)
Oropharyngeal pain * 1	1/2364 (0.04%)	0/2405 (0.00%)
Pleural effusion * 1	1/2364 (0.04%)	0/2405 (0.00%)
Pneumonia aspiration * 1	2/2364 (0.08%)	0/2405 (0.00%)
Pneumonitis * 1	2/2364 (0.08%)	4/2405 (0.17%)
Pneumothorax * 1	1/2364 (0.04%)	3/2405 (0.12%)
Pulmonary embolism * 1	5/2364 (0.21%)	5/2405 (0.21%)
Pulmonary fibrosis * 1	1/2364 (0.04%)	1/2405 (0.04%)
Skin and subcutaneous tissue disorders
Acute febrile neutrophilic dermatosis * 1	0/2364 (0.00%)	1/2405 (0.04%)
Angioedema * 1	0/2364 (0.00%)	1/2405 (0.04%)
Dermatitis acneiform * 1	1/2364 (0.04%)	0/2405 (0.00%)
Dermatitis exfoliative * 1	1/2364 (0.04%)	0/2405 (0.00%)
Erythema * 1	1/2364 (0.04%)	0/2405 (0.00%)
Palmar-plantar erythrodysaesthesia syndrome * 1	1/2364 (0.04%)	1/2405 (0.04%)
Rash * 1	5/2364 (0.21%)	1/2405 (0.04%)
Rash macular * 1	0/2364 (0.00%)	1/2405 (0.04%)
Rash maculo-papular * 1	1/2364 (0.04%)	1/2405 (0.04%)
Skin ulcer * 1	1/2364 (0.04%)	0/2405 (0.00%)
Toxic skin eruption * 1	1/2364 (0.04%)	0/2405 (0.00%)
Urticaria * 1	1/2364 (0.04%)	0/2405 (0.00%)
Surgical and medical procedures
Hospitalisation * 1	0/2364 (0.00%)	1/2405 (0.04%)
Vascular disorders
Axillary vein thrombosis * 1	0/2364 (0.00%)	1/2405 (0.04%)
Deep vein thrombosis * 1	2/2364 (0.08%)	1/2405 (0.04%)
Embolism * 1	3/2364 (0.13%)	3/2405 (0.12%)
Embolism venous * 1	1/2364 (0.04%)	0/2405 (0.00%)
Haematoma * 1	0/2364 (0.00%)	1/2405 (0.04%)
Haemorrhage * 1	0/2364 (0.00%)	1/2405 (0.04%)
Hypertension * 1	1/2364 (0.04%)	4/2405 (0.17%)
Hypotension * 1	2/2364 (0.08%)	5/2405 (0.21%)
Jugular vein thrombosis * 1	1/2364 (0.04%)	1/2405 (0.04%)
Lymphoedema * 1	1/2364 (0.04%)	1/2405 (0.04%)
Phlebitis * 1	1/2364 (0.04%)	1/2405 (0.04%)
Subclavian vein thrombosis * 1	1/2364 (0.04%)	1/2405 (0.04%)
Thrombophlebitis * 1	1/2364 (0.04%)	2/2405 (0.08%)
Thrombosis * 1	0/2364 (0.00%)	3/2405 (0.12%)
Varicose vein * 1	1/2364 (0.04%)	0/2405 (0.00%)
Venous thrombosis limb * 1	2/2364 (0.08%)	0/2405 (0.00%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 19.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pertuzumab + Trastuzumab + Chemotherapy	Placebo + Trastuzumab + Chemotherapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	2350/2364 (99.41%)	2370/2405 (98.54%)
Blood and lymphatic system disorders
Anaemia * 1	648/2364 (27.41%)	553/2405 (22.99%)
Leukopenia * 1	214/2364 (9.05%)	220/2405 (9.15%)
Neutropenia * 1	574/2364 (24.28%)	538/2405 (22.37%)
Eye disorders
Dry eye * 1	140/2364 (5.92%)	112/2405 (4.66%)
Lacrimation increased * 1	310/2364 (13.11%)	322/2405 (13.39%)
Gastrointestinal disorders
Abdominal pain * 1	281/2364 (11.89%)	255/2405 (10.60%)
Abdominal pain upper * 1	241/2364 (10.19%)	217/2405 (9.02%)
Constipation * 1	681/2364 (28.81%)	758/2405 (31.52%)
Diarrhoea * 1	1657/2364 (70.09%)	1078/2405 (44.82%)
Dry mouth * 1	148/2364 (6.26%)	136/2405 (5.65%)
Dyspepsia * 1	325/2364 (13.75%)	341/2405 (14.18%)
Gastrooesophageal reflux disease * 1	120/2364 (5.08%)	107/2405 (4.45%)
Haemorrhoids * 1	183/2364 (7.74%)	124/2405 (5.16%)
Nausea * 1	1628/2364 (68.87%)	1571/2405 (65.32%)
Stomatitis * 1	665/2364 (28.13%)	572/2405 (23.78%)
Vomiting * 1	761/2364 (32.19%)	725/2405 (30.15%)
General disorders
Asthenia * 1	504/2364 (21.32%)	499/2405 (20.75%)
Fatigue * 1	1150/2364 (48.65%)	1063/2405 (44.20%)
Influenza like illness * 1	125/2364 (5.29%)	119/2405 (4.95%)
Mucosal inflammation * 1	549/2364 (23.22%)	447/2405 (18.59%)
Oedema peripheral * 1	405/2364 (17.13%)	483/2405 (20.08%)
Pain * 1	157/2364 (6.64%)	165/2405 (6.86%)
Pyrexia * 1	446/2364 (18.87%)	433/2405 (18.00%)
Oedema * 1	139/2364 (5.88%)	156/2405 (6.49%)
Infections and infestations
Conjunctivitis * 1	147/2364 (6.22%)	124/2405 (5.16%)
Nasopharyngitis * 1	315/2364 (13.32%)	284/2405 (11.81%)
Rhinitis * 1	141/2364 (5.96%)	116/2405 (4.82%)
Upper respiratory tract infection * 1	184/2364 (7.78%)	173/2405 (7.19%)
Urinary tract infection * 1	180/2364 (7.61%)	155/2405 (6.44%)
Injury, poisoning and procedural complications
Radiation skin injury * 1	297/2364 (12.56%)	266/2405 (11.06%)
Investigations
Alanine aminotransferase increased * 1	220/2364 (9.31%)	242/2405 (10.06%)
Aspartate aminotransferase increased * 1	145/2364 (6.13%)	162/2405 (6.74%)
Ejection fraction decreased * 1	115/2364 (4.86%)	142/2405 (5.90%)
Neutrophil count decreased * 1	324/2364 (13.71%)	329/2405 (13.68%)
Weight decreased * 1	191/2364 (8.08%)	76/2405 (3.16%)
Weight increased * 1	59/2364 (2.50%)	130/2405 (5.41%)
White blood cell count decreased * 1	233/2364 (9.86%)	206/2405 (8.57%)
Metabolism and nutrition disorders
Decreased appetite * 1	561/2364 (23.73%)	478/2405 (19.88%)
Hypomagnesaemia * 1	145/2364 (6.13%)	78/2405 (3.24%)
Hypokalaemia * 1	150/2364 (6.35%)	97/2405 (4.03%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	678/2364 (28.68%)	781/2405 (32.47%)
Back pain * 1	207/2364 (8.76%)	237/2405 (9.85%)
Bone pain * 1	223/2364 (9.43%)	256/2405 (10.64%)
Muscle spasms * 1	217/2364 (9.18%)	123/2405 (5.11%)
Musculoskeletal pain * 1	201/2364 (8.50%)	215/2405 (8.94%)
Myalgia * 1	613/2364 (25.93%)	708/2405 (29.44%)
Pain in extremity * 1	234/2364 (9.90%)	252/2405 (10.48%)
Nervous system disorders
Dizziness * 1	269/2364 (11.38%)	274/2405 (11.39%)
Dysgeusia * 1	614/2364 (25.97%)	518/2405 (21.54%)
Headache * 1	531/2364 (22.46%)	561/2405 (23.33%)
Neuropathy peripheral * 1	365/2364 (15.44%)	369/2405 (15.34%)
Paraesthesia * 1	276/2364 (11.68%)	239/2405 (9.94%)
Peripheral sensory neuropathy * 1	426/2364 (18.02%)	422/2405 (17.55%)
Psychiatric disorders
Anxiety * 1	151/2364 (6.39%)	109/2405 (4.53%)
Insomnia * 1	404/2364 (17.09%)	400/2405 (16.63%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	372/2364 (15.74%)	349/2405 (14.51%)
Dyspnoea * 1	279/2364 (11.80%)	272/2405 (11.31%)
Epistaxis * 1	428/2364 (18.10%)	325/2405 (13.51%)
Oropharyngeal pain * 1	215/2364 (9.09%)	175/2405 (7.28%)
Rhinorrhoea * 1	191/2364 (8.08%)	135/2405 (5.61%)
Skin and subcutaneous tissue disorders
Alopecia * 1	1577/2364 (66.71%)	1610/2405 (66.94%)
Dry skin * 1	311/2364 (13.16%)	268/2405 (11.14%)
Erythema * 1	234/2364 (9.90%)	214/2405 (8.90%)
Nail discolouration * 1	175/2364 (7.40%)	178/2405 (7.40%)
Nail disorder * 1	280/2364 (11.84%)	284/2405 (11.81%)
Palmar-plantar erythrodysaesthesia syndrome * 1	216/2364 (9.14%)	157/2405 (6.53%)
Pruritus * 1	331/2364 (14.00%)	217/2405 (9.02%)
Rash * 1	604/2364 (25.55%)	487/2405 (20.25%)
Vascular disorders
Hot flush * 1	482/2364 (20.39%)	509/2405 (21.16%)
Hypertension * 1	91/2364 (3.85%)	122/2405 (5.07%)
Lymphoedema * 1	133/2364 (5.63%)	160/2405 (6.65%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 19.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

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

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

Results Point of Contact

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

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

Gelber RD, Wang XV, Cole BF, Cameron D, Cardoso F, Tjan-Heijnen V, Krop I, Loi S, Salgado R, Kiermaier A, Frank E, Fumagalli D, Caballero C, de Azambuja E, Procter M, Clark E, Restuccia E, Heeson S, Bines J, Loibl S, Piccart-Gebhart M; APHINITY Steering Committee and Investigators. Six-year absolute invasive disease-free survival benefit of adding adjuvant pertuzumab to trastuzumab and chemotherapy for patients with early HER2-positive breast cancer: A Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of the APHINITY (BIG 4-11) trial. Eur J Cancer. 2022 May;166:219-228. doi: 10.1016/j.ejca.2022.01.031. Epub 2022 Mar 18.

Bines J, Clark E, Barton C, Restuccia E, Procter M, Sonnenblick A, Fumagalli D, Parlier D, Arahmani A, Baselga J, Viale G, Reaby LL, Frank E, Gelber RD, Piccart M, Jackisch C, Petersen JA. Patient-reported function, health-related quality of life, and symptoms in APHINITY: pertuzumab plus trastuzumab and chemotherapy in HER2-positive early breast cancer. Br J Cancer. 2021 Jul;125(1):38-47. doi: 10.1038/s41416-021-01323-y. Epub 2021 Apr 7.

Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pienkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. doi: 10.1200/JCO.20.01204. Epub 2021 Feb 4.

Bines J, Procter M, Restuccia E, Viale G, Zardavas D, Suter T, Arahmani A, Van Dooren V, Baselga J, Clark E, Eng-Wong J, Gelber RD, Piccart M, Mobus V, de Azambuja E; APHINITY Steering Committee and Investigators. Incidence and Management of Diarrhea With Adjuvant Pertuzumab and Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. Clin Breast Cancer. 2020 Apr;20(2):174-181.e3. doi: 10.1016/j.clbc.2019.06.016. Epub 2019 Sep 5.

Luo Y, Li W, Jiang Z, Zhang Q, Wang L, Mao Y, Tjan-Heijnen VCG, Im SA, McConnell R, Bejarano S, Fumagalli D, Bines J, Wang B, Garg A, Kirschbrown WP, Xu B. Pharmacokinetics of pertuzumab administered concurrently with trastuzumab in Chinese patients with HER2-positive early breast cancer. Anticancer Drugs. 2019 Sep;30(8):866-872. doi: 10.1097/CAD.0000000000000808.

Kirschbrown WP, Kagedal M, Wang B, Lindbom L, Knott A, Mack R, Monemi S, Nijem I, Girish S, Freeman C, Fumagalli D, McConnell R, Jerusalem G, Twelves C, Baselga J, von Minckwitz G, Bines J, Garg A. Pharmacokinetic and exploratory exposure-response analysis of pertuzumab in patients with operable HER2-positive early breast cancer in the APHINITY study. Cancer Chemother Pharmacol. 2019 Jun;83(6):1147-1158. doi: 10.1007/s00280-019-03826-1. Epub 2019 Apr 11.

von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. doi: 10.1056/NEJMoa1703643. Epub 2017 Jun 5. Erratum In: N Engl J Med. 2017 Aug 17;377(7):702. N Engl J Med. 2018 Oct 18;379(16):1585.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01358877
• Other Study ID Numbers: BO25126; TOC4939G ( Other Identifier: Genentech ); 2010-022902-41 ( EudraCT Number ); BIG 4-11 ( Other Identifier: Breast International Group )
• First Submitted: May 20, 2011
• First Posted: May 24, 2011
• Results First Submitted: December 4, 2017
• Results First Posted: January 5, 2018
• Last Update Posted: April 10, 2024