Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01358877
Recruitment Status : Active, not recruiting
First Posted : May 24, 2011
Results First Posted : January 5, 2018
Last Update Posted : June 21, 2019
Sponsor:
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
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
Hide 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.
Arm/Group Title Pertuzumab + Trastuzumab + Chemotherapy Placebo + Trastuzumab + Chemotherapy Total
Hide 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
Hide 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
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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Pertuzumab + Trastuzumab + Chemotherapy Placebo + Trastuzumab + Chemotherapy
Hide 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
Show Statistical Analysis 1 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Pertuzumab + Trastuzumab + Chemotherapy Placebo + Trastuzumab + Chemotherapy
Hide 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
Show Statistical Analysis 1 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Pertuzumab + Trastuzumab + Chemotherapy Placebo + Trastuzumab + Chemotherapy
Hide 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
Show Statistical Analysis 1 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Pertuzumab + Trastuzumab + Chemotherapy Placebo + Trastuzumab + Chemotherapy
Hide 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
Show Statistical Analysis 1 Hide 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
Hide Description The Kaplan-Meier approach was used to estimate the percentage of participants who were alive at 3 years.
Time Frame 3 years
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Pertuzumab + Trastuzumab + Chemotherapy Placebo + Trastuzumab + Chemotherapy
Hide 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
Show Statistical Analysis 1 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Pertuzumab + Trastuzumab + Chemotherapy Placebo + Trastuzumab + Chemotherapy
Hide 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
Show Statistical Analysis 1 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Show Statistical Analysis 1 Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Pertuzumab + Trastuzumab + Chemotherapy Placebo + Trastuzumab + Chemotherapy
Hide 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
Show Statistical Analysis 1 Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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)
Show Statistical Analysis 1 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide Description [Not Specified]
Time Frame Cycles 1, 10 and 15 (Cycle length=21 days)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide Description [Not Specified]
Time Frame Cycles 1, 10 and 15 (Cycle length=21 days)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide Description [Not Specified]
Time Frame Cycles 1, 10 and 15 (Cycle length=21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable participants. Number analyzed=participants evaluable for this outcome measure at specified timepoint.
Arm/Group Title Pertuzumab + Trastuzumab + Chemotherapy
Hide 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
Hide Description [Not Specified]
Time Frame Cycles 1, 10 and 15 (Cycle length=21 days)
Hide Outcome Measure Data
Hide 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
Hide 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)
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
Hide 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   --/--   --/-- 
Show Serious Adverse Events Hide 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