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A Study of Pertuzumab in Combination With Trastuzumab (Herceptin) and a Taxane in First-Line Treatment in Participants With Human Epidermal Growth Factor 2 (HER2)-Positive Advanced Breast Cancer (PERUSE)

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: NCT01572038
Recruitment Status : Completed
First Posted : April 5, 2012
Results First Posted : September 25, 2020
Last Update Posted : September 25, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Neoplasms
Interventions Drug: Docetaxel
Drug: Nab-paclitaxel
Drug: Paclitaxel
Drug: Pertuzumab
Drug: Trastuzumab
Enrollment 1436
Recruitment Details  
Pre-assignment Details A total of 1697 patients were screened: 261 failed screening and 1436 were enrolled in the study.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Period Title: Overall Study
Started [1] 1436 [2]
Received at Least One Dose of Study Drug [3] 1436
Completed 445
Not Completed 991
Reason Not Completed
Death             648
Withdrawal by Subject             204
Lost to Follow-up             81
Physician Decision             20
Patient Decision             14
Progressive Disease             8
Site Closed Before Completing Form             6
Enrolled into Another Trial             3
Participated in Another Trial             3
Termination by Sponsor             2
Patient Deterioration             1
Sponsor Decision             1
[1]
Intent-to-Treat (ITT) Population
[2]
All participants who were enrolled in the study.
[3]
Safety Population
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Baseline Participants 1436
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1436 participants
54.4  (12.10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1436 participants
Female
1429
  99.5%
Male
7
   0.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1436 participants
Caucasian
1032
  71.9%
Black
9
   0.6%
Asian
88
   6.1%
Native American
28
   1.9%
Other
57
   4.0%
Not Applicable as per Local Regulations
222
  15.5%
Age Categorical (≤65 or >65 Years Old)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1436 participants
≤65 Years Old
1167
  81.3%
>65 Years Old
269
  18.7%
Ethnicity  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1436 participants
Hispanic/Latino
269
  18.7%
Chinese
57
   4.0%
Japanese
2
   0.1%
Mixed Ethnicity
18
   1.3%
Indian
21
   1.5%
Other
495
  34.5%
Not Applicable as per Local Regulations
574
  40.0%
Geographic Region of Enrollment   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1436 participants
Europe
1009
  70.3%
Asia
177
  12.3%
North America
34
   2.4%
South America
121
   8.4%
Africa
71
   4.9%
Other (Australia)
24
   1.7%
[1]
Measure Description: Geographic region of enrollment was categorized as follows: Europe = Austria, Belgium, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Lithuania, Netherlands, Poland, Portugal, Serbia, Slovenia, Spain, Sweden, United Kingdom, Ukraine; Asia = China, Hong Kong, Israel, Lebanon, Pakistan, Saudi Arabia, Turkey, United Arab Emirates; North America = Canada; South America = Argentina, Brazil, Ecuador, Mexico, Peru, Uruguay, Venezuela; Africa = Algeria, Egypt, Morocco; and Other = Australia.
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1436 participants
Grade 0 or 1
1371
  95.5%
Grade 2
63
   4.4%
Missing
2
   0.1%
[1]
Measure Description: Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; Grade 2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
Visceral Disease at Baseline   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1436 participants
Visceral Disease
992
  69.1%
Non-visceral Disease
444
  30.9%
[1]
Measure Description: The disease was considered as "visceral" if at least one lesion in a location other than breast, bone, bone marrow, lymph nodes, skin and soft tissue was observed during baseline tumor assessment. The disease was considered as "non-visceral" if all lesions observed at baseline were localized in breast, bone, bone marrow, lymph nodes, skin and soft tissue.
Hormone Receptor Status of Disease at Baseline   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1436 participants
Positive
918
  63.9%
Negative
512
  35.7%
Unknown
6
   0.4%
[1]
Measure Description: Hormone receptor status of the primary tumor and metastatic disease (combined) was defined as follows: Positive: if either estrogen receptor (ER) or progesterone receptor (PgR) status was positive; Negative: if both ER and PgR status was negative; Unknown: if both the ER and PgR status was unknown.
Prior Neoadjuvant or Adjuvant Chemotherapy Received  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1436 participants
Prior (Neo)Adjuvant Chemotherapy
786
  54.7%
No Prior (Neo)Adjuvant Chemotherapy
650
  45.3%
Previous Trastuzumab Therapy Received for Breast Cancer  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1436 participants
Previous Trastuzumab Therapy
400
  27.9%
No Previous Trastuzumab Therapy
1036
  72.1%
Initial Type of Taxane Received During the Study: Docetaxel, Paclitaxel, or Nab-Paclitaxel  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1436 participants
Docetaxel
775
  54.0%
Paclitaxel
588
  40.9%
Nab-Paclitaxel
65
   4.5%
None
8
   0.6%
Measurable or Non-Measurable Disease (per RECIST v1.1) at Baseline  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1436 participants
Measurable Disease
1198
  83.4%
Non-Measurable Disease
238
  16.6%
1.Primary Outcome
Title Overview of the Number of Participants With at Least One Treatment-Emergent Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0)
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. TEAEs to monitor included anaphylaxis and hypersensitivity, cardiac dysfunction, diarrhoea Grade ≥3, pregnancy-related AEs, interstitial lung disease, infusion-/administration-related reactions, mucositis, (febrile) neutropenia, rash/skin reactions, and suspected transmission of infectious agent. TEAEs of special interest included LVEF decreased, liver enzymes increased, and suspected transmission of infectious agent by the study drug.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE - Any Grade
1419
  98.8%
Any TEAE - Grade 3 or Higher (≥3)
879
  61.2%
Any Serious TEAE
535
  37.3%
Any TEAE Leading to Death
31
   2.2%
Any TEAE Related to Pertuzumab - Any Grade
1037
  72.2%
Any TEAE Related to Trastuzumab - Any Grade
946
  65.9%
Any TEAE Related to Taxane - Any Grade
1342
  93.5%
Any TEAE Related to Pertuzumab - Grade ≥3
286
  19.9%
Any TEAE Related to Trastuzumab - Grade ≥3
245
  17.1%
Any TEAE Related to Taxane - Grade ≥3
514
  35.8%
Any TEAE Leading to Interruption of Pertuzumab
334
  23.3%
Any TEAE Leading to Interruption of Trastuzumab
386
  26.9%
Any TEAE Leading to Interruption of Taxane
354
  24.7%
Any TEAE Leading to Discontinuation of Pertuzumab
140
   9.7%
Any TEAE Leading to Discontinuation of Trastuzumab
133
   9.3%
Any TEAE Leading to Discontinuation of Taxane
286
  19.9%
Any TEAE to Monitor - Any Grade
1320
  91.9%
Any TEAE to Monitor - Grade ≥3
535
  37.3%
Any TEAE of Special Interest
91
   6.3%
Any TEAE Within 28 Days of Treatmt Discontinuation
975
  67.9%
2.Primary Outcome
Title Number of Participants Who Died Over the Course of the Study by Reported Cause of Death (Adverse Events Leading to Death by System Organ Class and Preferred Term)
Hide Description All adverse events leading to death, regardless of whether they were classified as treatment emergent, are listed by system organ class (SOC) and preferred term (PT) according to the Medical Dictionary for Regulatory Activities, version 22.1 (MedDRA version 22.1); PTs that are part of a given SOC are listed in the rows directly below each SOC within the results table. Admin. = administration; Mediast. = mediastinal
Time Frame The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Total Number of Deaths
658
  45.8%
Number of Deaths by Cause: Progressive Disease
581
  40.5%
Number of Deaths by Cause: Other
42
   2.9%
Number of Deaths by Cause: Adverse Event (Total)
35
   2.4%
Infections and Infestations (SOC)
11
   0.8%
Peritonitis (PT)
1
   0.1%
Pneumonia (PT)
5
   0.3%
Respiratory Tract Infection (PT)
1
   0.1%
Sepsis (PT)
3
   0.2%
Septic Shock (PT)
1
   0.1%
Cardiac Disorders (SOC)
7
   0.5%
Cardiac Arrest (PT)
2
   0.1%
Cardiac Failure (PT)
1
   0.1%
Cardiac Failure Congestive (PT)
1
   0.1%
Cardio-respiratory Arrest (PT)
1
   0.1%
Myocardial Infarction (PT)
1
   0.1%
Right Ventricular Failure (PT)
1
   0.1%
General Disorders & Admin. Site Conditions (SOC)
6
   0.4%
Death (PT)
6
   0.4%
Blood and Lymphatic System Disorders (SOC)
3
   0.2%
Febrile Neutropenia (PT)
1
   0.1%
Neutropenia (PT)
1
   0.1%
Thrombocytopenia (PT)
1
   0.1%
Respiratory, Thoracic & Mediast. Disorders (SOC)
3
   0.2%
Acute Respiratory Distress Syndrome (PT)
1
   0.1%
Aspiration (PT)
1
   0.1%
Pneumonitis (PT)
1
   0.1%
Gastrointestinal Disorders (SOC)
2
   0.1%
Pancreatitis (PT)
1
   0.1%
Pancreatitis Chronic (PT)
1
   0.1%
Nervous System Disorders (SOC)
2
   0.1%
Hepatic Encephalopathy (PT)
1
   0.1%
Ischemic Stroke (PT)
1
   0.1%
Metabolism and Nutrition Disorders (SOC)
1
   0.1%
Hypoglycaemia (PT)
1
   0.1%
Hepatobiliary Disorders (SOC)
1
   0.1%
Hepatic Failure (PT)
1
   0.1%
Psychiatric Disorders (SOC)
1
   0.1%
Delirium (PT)
1
   0.1%
3.Primary Outcome
Title Number of Participants Who Died Within 6 Months of Starting Study Treatment by Reported Cause of Death (Adverse Events Leading to Death by System Organ Class and Preferred Term)
Hide Description All adverse events leading to death, regardless of whether they were classified as treatment emergent, are listed by system organ class (SOC) and preferred term (PT) according to the Medical Dictionary for Regulatory Activities, version 22.1 (MedDRA version 22.1); PTs that are part of a given SOC are listed in the rows directly below each SOC within the results table. Admin. = administration; Mediast. = mediastinal
Time Frame The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Total Number of Deaths
38
   2.6%
Number of Deaths by Cause: Progressive Disease
18
   1.3%
Number of Deaths by Cause: Other
1
   0.1%
Number of Deaths by Cause: Adverse Event (Total)
19
   1.3%
Infections and Infestations (SOC)
6
   0.4%
Peritonitis (PT)
1
   0.1%
Pneumonia (PT)
2
   0.1%
Respiratory Tract Infection (PT)
1
   0.1%
Sepsis (PT)
2
   0.1%
General Disorders & Admin. Site Conditions (SOC)
4
   0.3%
Death (PT)
4
   0.3%
Blood and Lymphatic System Disorders (SOC)
3
   0.2%
Febrile Neutropenia (PT)
1
   0.1%
Neutropenia (PT)
1
   0.1%
Thrombocytopenia (PT)
1
   0.1%
Cardiac Disorders (SOC)
2
   0.1%
Cardiac Arrest (PT)
1
   0.1%
Cardio-Respiratory Arrest (PT)
1
   0.1%
Respiratory, Thoracic & Mediast. Disorders (SOC)
2
   0.1%
Acute Respiratory Distress Syndrome (PT)
1
   0.1%
Pneumonitis (PT)
1
   0.1%
Gastrointestinal Disorders (SOC)
1
   0.1%
Pancreatitis (PT)
1
   0.1%
Nervous System Disorders (SOC)
1
   0.1%
Hepatic Encephalopathy (PT)
1
   0.1%
Metabolism and Nutrition Disorders (SOC)
1
   0.1%
Hypoglycaemia (PT)
1
   0.1%
Hepatobiliary Disorders (SOC)
1
   0.1%
Hepatic Failure (PT)
1
   0.1%
4.Primary Outcome
Title Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events, Occurring in ≥1% of Participants by System Organ Class and Preferred Term
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. MedDRA version 22.1 was used to code AEs by system organ class (SOC) and preferred term (PT); PTs that are part of a given SOC are listed in the rows directly below each SOC within the results table. If a participant experienced the same AE at more than one severity grade, only the most severe grade was presented.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE - Grade (Gr.) 3
676
  47.1%
Any TEAE - Gr. 4
172
  12.0%
Any TEAE - Gr. 5
31
   2.2%
Gastrointestinal Disorders (SOC) - Gr. 3
163
  11.4%
Gastrointestinal Disorders (SOC) - Gr. 4
4
   0.3%
Gastrointestinal Disorders (SOC) - Gr. 5
2
   0.1%
Diarrhoea (PT) - Gr. 3
119
   8.3%
Diarrhoea (PT) - Gr. 4
1
   0.1%
Diarrhoea (PT) - Gr. 5
0
   0.0%
Vomiting (PT) - Gr. 3
19
   1.3%
Vomiting (PT) - Gr. 4
0
   0.0%
Vomiting (PT) - Gr. 5
0
   0.0%
Skin & Subcutaneous Tissue Disorders (SOC) - Gr. 3
56
   3.9%
Skin & Subcutaneous Tissue Disorders (SOC) - Gr. 4
0
   0.0%
Skin & Subcutaneous Tissue Disorders (SOC) - Gr. 5
0
   0.0%
Gen. Disorders & Admin.Site Conditions (SOC)-Gr. 3
100
   7.0%
Gen. Disorders & Admin.Site Conditions (SOC)-Gr. 4
0
   0.0%
Gen. Disorders & Admin.Site Conditions (SOC)-Gr. 5
3
   0.2%
Fatigue (PT) - Gr. 3
36
   2.5%
Fatigue (PT) - Gr. 4
0
   0.0%
Fatigue (PT) - Gr. 5
0
   0.0%
Asthenia (PT) - Gr. 3
29
   2.0%
Asthenia (PT) - Gr. 4
0
   0.0%
Asthenia (PT) - Gr. 5
0
   0.0%
Mucosal Inflammation (PT) - Gr. 3
14
   1.0%
Mucosal Inflammation (PT) - Gr. 4
0
   0.0%
Mucosal Inflammation (PT) - Gr. 5
0
   0.0%
Nervous System Disorders (SOC) - Gr. 3
139
   9.7%
Nervous System Disorders (SOC) - Gr. 4
0
   0.0%
Nervous System Disorders (SOC) - Gr. 5
2
   0.1%
Neuropathy Peripheral (PT) - Gr. 3
26
   1.8%
Neuropathy Peripheral (PT) - Gr. 4
0
   0.0%
Neuropathy Peripheral (PT) - Gr. 5
0
   0.0%
Syncope (PT) - Gr. 3
24
   1.7%
Syncope (PT) - Gr. 4
0
   0.0%
Syncope (PT) - Gr. 5
0
   0.0%
Headache (PT) - Gr. 3
17
   1.2%
Headache (PT) - Gr. 4
0
   0.0%
Headache (PT) - Gr. 5
0
   0.0%
Paraesthesia (PT) - Gr. 3
14
   1.0%
Paraesthesia (PT) - Gr. 4
0
   0.0%
Paraesthesia (PT) - Gr. 5
0
   0.0%
Peripheral Sensory Neuropathy (PT) - Gr. 3
14
   1.0%
Peripheral Sensory Neuropathy (PT) - Gr. 4
0
   0.0%
Peripheral Sensory Neuropathy (PT) - Gr. 5
0
   0.0%
Infections and Infestations (SOC) - Gr. 3
148
  10.3%
Infections and Infestations (SOC) - Gr. 4
19
   1.3%
Infections and Infestations (SOC) - Gr. 5
10
   0.7%
Pneumonia (PT) - Gr. 3
22
   1.5%
Pneumonia (PT) - Gr. 4
1
   0.1%
Pneumonia (PT) - Gr. 5
4
   0.3%
Vascular Device Infection (PT) - Gr. 3
14
   1.0%
Vascular Device Infection (PT) - Gr. 4
0
   0.0%
Vascular Device Infection (PT) - Gr. 5
0
   0.0%
Device Related Infection (PT) - Gr. 3
14
   1.0%
Device Related Infection (PT) - Gr. 4
0
   0.0%
Device Related Infection (PT) - Gr. 5
0
   0.0%
Musculo. & Connective Tissue Disorders (SOC)-Gr. 3
75
   5.2%
Musculo. & Connective Tissue Disorders (SOC)-Gr. 4
0
   0.0%
Musculo. & Connective Tissue Disorders (SOC)-Gr. 5
0
   0.0%
Resp., Thoracic & Mediast. Disorders (SOC) - Gr. 3
62
   4.3%
Resp., Thoracic & Mediast. Disorders (SOC) - Gr. 4
5
   0.3%
Resp., Thoracic & Mediast. Disorders (SOC) - Gr. 5
3
   0.2%
Pulmonary Embolism (PT) - Gr. 3
21
   1.5%
Pulmonary Embolism (PT) - Gr. 4
2
   0.1%
Pulmonary Embolism (PT) - Gr. 5
0
   0.0%
Dyspnoea (PT) - Gr. 3
19
   1.3%
Dyspnoea (PT) - Gr. 4
1
   0.1%
Dyspnoea (PT) - Gr. 5
0
   0.0%
Blood & Lymphatic System Disorders (SOC) - Gr. 3
158
  11.0%
Blood & Lymphatic System Disorders (SOC) - Gr. 4
104
   7.2%
Blood & Lymphatic System Disorders (SOC) - Gr. 5
3
   0.2%
Neutropenia (PT) - Gr. 3
77
   5.4%
Neutropenia (PT) - Gr. 4
67
   4.7%
Neutropenia (PT) - Gr. 5
1
   0.1%
Febrile Neutropenia (PT) - Gr. 3
51
   3.6%
Febrile Neutropenia (PT) - Gr. 4
38
   2.6%
Febrile Neutropenia (PT) - Gr. 5
1
   0.1%
Anaemia (PT) - Gr. 3
29
   2.0%
Anaemia (PT) - Gr. 4
0
   0.0%
Anaemia (PT) - Gr. 5
0
   0.0%
Leukopenia (PT) - Gr. 3
15
   1.0%
Leukopenia (PT) - Gr. 4
3
   0.2%
Leukopenia (PT) - Gr. 5
0
   0.0%
Investigations (SOC) - Gr. 3
116
   8.1%
Investigations (SOC) - Gr. 4
20
   1.4%
Investigations (SOC) - Gr. 5
0
   0.0%
Neutrophil Count Decreased (PT) - Gr. 3
25
   1.7%
Neutrophil Count Decreased (PT) - Gr. 4
13
   0.9%
Neutrophil Count Decreased (PT) - Gr. 5
0
   0.0%
Ejection Fraction Decreased (PT) - Gr. 3
22
   1.5%
Ejection Fraction Decreased (PT) - Gr. 4
2
   0.1%
Ejection Fraction Decreased (PT) - Gr. 5
0
   0.0%
Gamma-Glutamyltransferase Increased (PT) - Gr. 3
19
   1.3%
Gamma-Glutamyltransferase Increased (PT) - Gr. 4
1
   0.1%
Gamma-Glutamyltransferase Increased (PT) - Gr. 5
0
   0.0%
White Blood Cell Count Decreased (PT) - Gr. 3
16
   1.1%
White Blood Cell Count Decreased (PT) - Gr. 4
2
   0.1%
White Blood Cell Count Decreased (PT) - Gr. 5
0
   0.0%
Alanine Aminotransferase Increased (PT) - Gr. 3
16
   1.1%
Alanine Aminotransferase Increased (PT) - Gr. 4
0
   0.0%
Alanine Aminotransferase Increased (PT) - Gr. 5
0
   0.0%
Metabolism and Nutrition Disorders (SOC) - Gr. 3
63
   4.4%
Metabolism and Nutrition Disorders (SOC) - Gr. 4
8
   0.6%
Metabolism and Nutrition Disorders (SOC) - Gr. 5
1
   0.1%
Hypokalaemia (PT) - Gr. 3
19
   1.3%
Hypokalaemia (PT) - Gr. 4
1
   0.1%
Hypokalaemia (PT) - Gr. 5
0
   0.0%
Vascular Disorders (SOC) - Gr. 3
62
   4.3%
Vascular Disorders (SOC) - Gr. 4
2
   0.1%
Vascular Disorders (SOC) - Gr. 5
0
   0.0%
Hypertension (PT) - Gr. 3
45
   3.1%
Hypertension (PT) - Gr. 4
1
   0.1%
Hypertension (PT) - Gr. 5
0
   0.0%
Psychiatric Disorders (SOC) - Gr. 3
15
   1.0%
Psychiatric Disorders (SOC) - Gr. 4
3
   0.2%
Psychiatric Disorders (SOC) - Gr. 5
1
   0.1%
Injury, Poisoning & Proced. Complicat. (SOC)-Gr. 3
43
   3.0%
Injury, Poisoning & Proced. Complicat. (SOC)-Gr. 4
6
   0.4%
Injury, Poisoning & Proced. Complicat. (SOC)-Gr. 5
0
   0.0%
Cardiac Disorders (SOC) - Gr. 3
35
   2.4%
Cardiac Disorders (SOC) - Gr. 4
5
   0.3%
Cardiac Disorders (SOC) - Gr. 5
7
   0.5%
Immune System Disorders (SOC) - Gr. 3
17
   1.2%
Immune System Disorders (SOC) - Gr. 4
1
   0.1%
Immune System Disorders (SOC) - Gr. 5
0
   0.0%
Renal and Urinary Disorders (SOC) - Gr. 3
15
   1.0%
Renal and Urinary Disorders (SOC) - Gr. 4
3
   0.2%
Renal and Urinary Disorders (SOC) - Gr. 5
0
   0.0%
Neoplasms Benign, Malignant & Unspec. (SOC) -Gr. 3
13
   0.9%
Neoplasms Benign, Malignant & Unspec. (SOC) -Gr. 4
5
   0.3%
Neoplasms Benign, Malignant & Unspec. (SOC) -Gr. 5
0
   0.0%
Hepatobiliary Disorders (SOC) - Gr. 3
13
   0.9%
Hepatobiliary Disorders (SOC) - Gr. 4
0
   0.0%
Hepatobiliary Disorders (SOC) - Gr. 5
1
   0.1%
5.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events of Any Grade That Were Related to Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥10% of Participants by System Organ Class
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. MedDRA version 22.1 was used to code AEs and the system organ classes are presented in descending order according to the total frequency of occurrence. If a participant experienced more than one event in a category, they were counted only once in that category.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE Related to Pertuzumab (Rel to Ptz)
1037
  72.2%
Rel to Ptz: Gastrointestinal Disorders
629
  43.8%
Rel to Ptz: Skin and Subcutaneous Tissue Disorders
491
  34.2%
Rel to Ptz: Gen. Disorders & Admin.Site Conditions
462
  32.2%
Rel to Ptz: Investigations
252
  17.5%
Rel to Ptz: Nervous System Disorders
207
  14.4%
Rel to Ptz: Resp., Thoracic & Mediast. Disorders
188
  13.1%
Rel to Ptz: Musculo. & Connective Tissue Disorders
184
  12.8%
Rel to Ptz: Blood & Lymphatic System Disorders
182
  12.7%
Rel to Ptz: Infections and Infestations
151
  10.5%
Any TEAE Related to Trastuzumab (Rel to Trz)
946
  65.9%
Rel to Trz: Gastrointestinal Disorders
435
  30.3%
Rel to Trz: Gen. Disorders & Admin.Site Conditions
434
  30.2%
Rel to Trz: Skin and Subcutaneous Tissue Disorders
384
  26.7%
Rel to Trz: Investigations
262
  18.2%
Rel to Trz: Nervous System Disorders
184
  12.8%
Rel to Trz: Musculo. & Connective Tissue Disorders
179
  12.5%
Rel to Trz: Blood & Lymphatic System Disorders
163
  11.4%
Rel to Trz: Resp., Thoracic & Mediast. Disorders
153
  10.7%
Any TEAE Related to Taxane (Rel to Tax)
1342
  93.5%
Rel to Tax: Gastrointestinal Disorders
984
  68.5%
Rel to Tax: Skin and Subcutaneous Tissue Disorders
938
  65.3%
Rel to Tax: Gen. Disorders & Admin.Site Conditions
834
  58.1%
Rel to Tax: Nervous System Disorders
764
  53.2%
Rel to Tax: Blood & Lymphatic System Disorders
457
  31.8%
Rel to Tax: Musculo. & Connective Tissue Disorders
386
  26.9%
Rel to Tax: Infections and Infestations
293
  20.4%
Rel to Tax: Resp., Thoracic & Mediast. Disorders
290
  20.2%
Rel to Tax: Metabolism and Nutrition Disorders
227
  15.8%
Rel to Tax: Investigations
201
  14.0%
Rel to Tax: Eye Disorders
174
  12.1%
6.Primary Outcome
Title Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events That Were Related to Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥0.5% of Participants by Preferred Term
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. MedDRA version 22.1 was used to code AEs and the preferred terms are presented in descending order according to the total frequency of occurrence. If a participant experienced more than one event in a category, they were counted only once in that category.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Any Grade ≥3 TEAE Related to Pertuz. (Rel to Ptz)
286
  19.9%
Rel to Ptz: Diarrhoea
59
   4.1%
Rel to Ptz: Neutropenia
28
   1.9%
Rel to Ptz: Febrile Neutropenia
28
   1.9%
Rel to Ptz: Ejection Fraction Decreased
19
   1.3%
Rel to Ptz: Neutrophil Count Decreased
15
   1.0%
Rel to Ptz: Fatigue
15
   1.0%
Rel to Ptz: Left Ventricular Dysfunction
10
   0.7%
Rel to Ptz: Asthenia
10
   0.7%
Rel to Ptz: White Blood Cell Count Decreased
10
   0.7%
Rel to Ptz: Cardiac Failure
9
   0.6%
Any Grade ≥3 TEAE Related to Trastuz. (Rel to Trz)
245
  17.1%
Rel to Trz: Diarrhoea
32
   2.2%
Rel to Trz: Neutropenia
30
   2.1%
Rel to Trz: Ejection Fraction Decreased
23
   1.6%
Rel to Trz: Febrile Neutropenia
21
   1.5%
Rel to Trz: Neutrophil Count Decreased
15
   1.0%
Rel to Trz: Fatigue
14
   1.0%
Rel to Trz: Left Ventricular Dysfunction
11
   0.8%
Rel to Trz: White Blood Cell Count Decreased
10
   0.7%
Rel to Trz: Cardiac Failure
8
   0.6%
Rel to Trz: Asthenia
8
   0.6%
Any Grade ≥3 TEAE Related to Taxane (Rel to Tax)
514
  35.8%
Rel to Tax: Neutropenia
140
   9.7%
Rel to Tax: Febrile Neutropenia
86
   6.0%
Rel to Tax: Diarrhoea
80
   5.6%
Rel to Tax: Neutrophil Count Decreased
34
   2.4%
Rel to Tax: Fatigue
26
   1.8%
Rel to Tax: Peripheral Neuropathy
24
   1.7%
Rel to Tax: Asthenia
20
   1.4%
Rel to Tax: Leukopenia
16
   1.1%
Rel to Tax: White Blood Cell Count Decreased
16
   1.1%
Rel to Tax: Mucosal Inflammation
14
   1.0%
Rel to Tax: Paraesthesia
13
   0.9%
Rel to Tax: Peripheral Sensory Neuropathy
13
   0.9%
Rel to Tax: Onycholysis
10
   0.7%
Rel to Tax: Neutropenic Sepsis
10
   0.7%
Rel to Tax: Anaemia
10
   0.7%
Rel to Tax: Vomiting
7
   0.5%
Rel to Tax: Neurotoxicity
7
   0.5%
7.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events Leading to Discontinuation of Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥0.2% of Participants by Preferred Term
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. MedDRA version 22.1 was used to code AEs and the preferred terms are presented in descending order according to the total frequency of occurrence. If a participant experienced more than one event in a category, they were counted only once in that category. Discont. = discontinuation; Ptz = pertuzumab; Tax = taxane; Trz = trastuzumab
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE, Pertuzumab Discontinuation (Ptz Discont)
140
   9.7%
Ptz Discont: Ejection Fraction Decreased
37
   2.6%
Ptz Discont: Cardiac Failure
10
   0.7%
Ptz Discont: Left Ventricular Dysfunction
7
   0.5%
Ptz Discont: Diarrhoea
7
   0.5%
Ptz Discont: Dyspnoea
4
   0.3%
Ptz Discont: Infusion Related Reaction
4
   0.3%
Ptz Discont: Sepsis
3
   0.2%
Ptz Discont: Neuropathy Peripheral
3
   0.2%
Ptz Discont: Hypersensitivity
3
   0.2%
Ptz Discont: General Physical Health Deterioration
3
   0.2%
Any TEAE, Trastuzumab Discontinuation(Trz Discont)
133
   9.3%
Trz Discont: Ejection Fraction Decreased
37
   2.6%
Trz Discont: Cardiac Failure
10
   0.7%
Trz Discont: Left Ventricular Dysfunction
7
   0.5%
Trz Discont: Diarrhoea
6
   0.4%
Trz Discont: Sepsis
3
   0.2%
Trz Discont: Dyspnoea
3
   0.2%
Trz Discont: Neuropathy Peripheral
3
   0.2%
Trz Discont: Hypersensitivity
3
   0.2%
Trz Discont: General Physical Health Deterioration
3
   0.2%
Any TEAE, Taxane Discontinuation (Tax Discont)
286
  19.9%
Tax Discont: Neuropathy Peripheral
52
   3.6%
Tax Discont: Peripheral Sensory Neuropathy
25
   1.7%
Tax Discont: Paraesthesia
24
   1.7%
Tax Discont: Diarrhoea
19
   1.3%
Tax Discont: Fatigue
16
   1.1%
Tax Discont: Asthenia
13
   0.9%
Tax Discont: Onycholysis
8
   0.6%
Tax Discont: Nail Toxicity
7
   0.5%
Tax Discont: Neurotoxicity
7
   0.5%
Tax Discont: Polyneuropathy
7
   0.5%
Tax Discont: Oedema Peripheral
7
   0.5%
Tax Discont: Febrile Neutropenia
7
   0.5%
Tax Discont: Neutropenia
7
   0.5%
Tax Discont: Dyspnoea
6
   0.4%
Tax Discont: Decreased Appetite
6
   0.4%
Tax Discont: Ejection Fraction Decreased
5
   0.3%
Tax Discont: General Physical Health Deterioration
4
   0.3%
Tax Discont: Mucosal Inflammation
4
   0.3%
Tax Discont: Rash
4
   0.3%
Tax Discont: Anaemia
4
   0.3%
Tax Discont: Arthralgia
4
   0.3%
Tax Discont: Drug Hypersensitivity
4
   0.3%
Tax Discont: Dysgeusia
3
   0.2%
Tax Discont: Nail Disorder
3
   0.2%
Tax Discont: Nail Dystrophy
3
   0.2%
Tax Discont: Skin Toxicity
3
   0.2%
Tax Discont: Pneumonia
3
   0.2%
Tax Discont: Sepsis
3
   0.2%
Tax Discont: Pleural Effusion
3
   0.2%
Tax Discont: Pneumonitis
3
   0.2%
Tax Discont: Cardiac Failure
3
   0.2%
Tax Discont: Myalgia
3
   0.2%
8.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events Leading to Dose Interruption of Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥0.5% of Participants by Preferred Term
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. MedDRA version 22.1 was used to code AEs and the preferred terms are presented in descending order according to the total frequency of occurrence. If a participant experienced more than one event in a category, they were counted only once in that category. Interrupt. = interruption; Ptz = pertuzumab; Tax = taxane; Trz = trastuzumab
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE, Pertuzumab Interruption (Ptz Interrupt)
334
  23.3%
Ptz Interrupt: Ejection Fraction Decreased
51
   3.6%
Ptz Interrupt: Diarrhoea
21
   1.5%
Ptz Interrupt: Neutropenia
17
   1.2%
Ptz Interrupt: Pneumonia
14
   1.0%
Ptz Interrupt: Upper Respiratory Tract Infection
13
   0.9%
Ptz Interrupt: Pyrexia
11
   0.8%
Ptz Interrupt: Dyspnoea
11
   0.8%
Ptz Interrupt: Drug Hypersensitivity
9
   0.6%
Ptz Interrupt: Influenza
8
   0.6%
Ptz Interrupt: Asthenia
8
   0.6%
Ptz Interrupt: Neutrophil Count Decreased
8
   0.6%
Ptz Interrupt: Nasopharyngitis
7
   0.5%
Ptz Interrupt: Anaemia
7
   0.5%
Any TEAE, Trastuzumab Interruption (Trz Interrupt)
386
  26.9%
Trz Interrupt: Ejection Fraction Decreased
52
   3.6%
Trz Interrupt: Drug Hypersensitivity
31
   2.2%
Trz Interrupt: Diarrhoea
20
   1.4%
Trz Interrupt: Pyrexia
18
   1.3%
Trz Interrupt: Neutropenia
17
   1.2%
Trz Interrupt: Dyspnoea
17
   1.2%
Trz Interrupt: Pneumonia
14
   1.0%
Trz Interrupt: Chills
13
   0.9%
Trz Interrupt: Infusion Related Reaction
13
   0.9%
Trz Interrupt: Upper Respiratory Tract Infection
12
   0.8%
Trz Interrupt: Neutrophil Count Decreased
8
   0.6%
Trz Interrupt: Influenza
7
   0.5%
Trz Interrupt: Asthenia
7
   0.5%
Trz Interrupt: Vomiting
7
   0.5%
Trz Interrupt: Anaemia
7
   0.5%
Trz Interrupt: Nasopharyngitis
7
   0.5%
Any TEAE, Taxane Interruption (Tax Interrupt)
354
  24.7%
Tax Interrupt: Neutropenia
46
   3.2%
Tax Interrupt: Diarrhoea
30
   2.1%
Tax Interrupt: Leukopenia
17
   1.2%
Tax Interrupt: Dyspnoea
15
   1.0%
Tax Interrupt: Pyrexia
14
   1.0%
Tax Interrupt: Neutrophil Count Decreased
14
   1.0%
Tax Interrupt: Ejection Fraction Decreased
13
   0.9%
Tax Interrupt: Neuropathy Peripheral
13
   0.9%
Tax Interrupt: Nasopharyngitis
10
   0.7%
Tax Interrupt: Drug Hypersensitivity
10
   0.7%
Tax Interrupt: Fatigue
10
   0.7%
Tax Interrupt: Upper Respiratory Tract Infection
9
   0.6%
Tax Interrupt: Infusion Related Reaction
9
   0.6%
Tax Interrupt: Asthenia
9
   0.6%
Tax Interrupt: Erythema
8
   0.6%
Tax Interrupt: Pneumonia
7
   0.5%
Tax Interrupt: Flushing
7
   0.5%
Tax Interrupt: Hypersensitivity
7
   0.5%
9.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events to Monitor of Any Grade, Occurring in ≥5% of Participants by Category
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first dose of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, it was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. If a participant had more than one event in a category, they were counted only once in that category. TEAEs to monitor included anaphylaxis and hypersensitivity, cardiac dysfunction, diarrhoea Grade ≥3, pregnancy-related AEs, interstitial lung disease, infusion-/administration-related reactions, mucositis, (febrile) neutropenia, rash/skin reactions, and suspected transmission of infectious agent. MedDRA version 22.1 was used to code AEs; AEs may fall within multiple categories.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
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Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
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Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE to Monitor
1320
  91.9%
Infusion-/Administration-Related Reactions
1096
  76.3%
Rash/Skin Reactions
668
  46.5%
Mucositis
618
  43.0%
Cardiac Dysfunction
478
  33.3%
Neutropenia/Febrile Neutropenia
439
  30.6%
Anaphylaxis and Hypersensitivity
124
   8.6%
Diarrhoea Grade ≥3
120
   8.4%
10.Primary Outcome
Title Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events to Monitor, Occurring in ≥0.5% of Participants by Category and Preferred Term
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first dose of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, it was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. If a participant had more than one event in a category, they were counted only once in that category. TEAEs to monitor included anaphylaxis and hypersensitivity, cardiac dysfunction, diarrhoea Grade ≥3, pregnancy-related AEs, interstitial lung disease, infusion-/administration-related reactions, mucositis, (febrile) neutropenia, rash/skin reactions, and suspected transmission of infectious agent. MedDRA version 22.1 was used to code AEs; preferred terms (PT) that are part of a given category are listed in the rows directly below each category within the results table.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
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Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
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Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Any Grade ≥3 TEAE to Monitor
535
  37.3%
Neutropenia/Febrile Neutropenia (Category)
279
  19.4%
Neutropenia (PT)
145
  10.1%
Febrile Neutropenia (PT)
90
   6.3%
Neutrophil Count Decreased (PT)
38
   2.6%
Leukopenia (PT)
18
   1.3%
White Blood Cell Count Decreased (PT)
18
   1.3%
Neutropenic Sepsis (PT)
10
   0.7%
Infusion-/Admin.-Related Reactions (Category)
123
   8.6%
Hypertension (PT)
27
   1.9%
IRR/ARR: Drug Hypersensitivity (PT)
12
   0.8%
Asthenia (PT)
11
   0.8%
Fatigue (PT)
11
   0.8%
Dyspnoea (PT)
10
   0.7%
Infusion Related Reaction (PT)
8
   0.6%
Paraesthesia (PT)
7
   0.5%
Diarrhoea Grade ≥3 (Category)
120
   8.4%
Diarrhoea (PT)
120
   8.4%
Cardiac Dysfunction (Category)
51
   3.6%
Ejection Fraction Decreased (PT)
24
   1.7%
Left Ventricular Dysfunction (PT)
11
   0.8%
Cardiac Failure (PT)
9
   0.6%
Mucositis (Category)
33
   2.3%
Mucosal Inflammation (PT)
14
   1.0%
Stomatitis (PT)
9
   0.6%
Rash/Skin Reactions (Category)
28
   1.9%
Rash (PT)
10
   0.7%
Anaphylaxis and Hypersensitivity (Category)
18
   1.3%
Anaphyl./Hypersens.: Drug Hypersensitivity (PT)
13
   0.9%
11.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events of Special Interest by Category and Preferred Term
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. TEAEs of special interest included LVEF decreased, liver enzymes (ALT or AST) increased, and suspected transmission of infectious agent by the study drug. MedDRA version 22.1 was used to code AEs; preferred terms (PT) that are part of a given category are listed in the rows directly below each category within the results table. If a participant experienced more than one event in a category, they were counted only once in that category.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
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Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
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Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE of Special Interest
91
   6.3%
Decline in LVEF (Category)
90
   6.3%
Ejection Fraction Decreased (PT)
75
   5.2%
Left Ventricular Dysfunction (PT)
8
   0.6%
Cardiac Failure (PT)
7
   0.5%
Cardiac Failure Congestive (PT)
1
   0.1%
Elevated ALT or AST (Category)
1
   0.1%
Hepatic Failure (PT)
1
   0.1%
12.Primary Outcome
Title Subgroup Analysis by Region of Enrollment: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
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Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Europe Asia North America South America Africa Other (Australia)
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Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1009 177 34 121 71 24
Measure Type: Count of Participants
Unit of Measure: Participants
Any Serious TEAE
385
  38.2%
74
  41.8%
9
  26.5%
37
  30.6%
16
  22.5%
14
  58.3%
Any TEAE - Grade 3 or Higher (≥3)
632
  62.6%
109
  61.6%
22
  64.7%
63
  52.1%
37
  52.1%
16
  66.7%
Any Grade ≥3 TEAE Related to Pertuzumab
187
  18.5%
44
  24.9%
5
  14.7%
27
  22.3%
19
  26.8%
4
  16.7%
13.Primary Outcome
Title Subgroup Analysis by Age (≤65 vs. >65 Years): Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), TEAEs Leading to Death, Grade ≥3 TEAEs, Any-Grade and Grade ≥3 TEAEs Related to Pertuzumab, and TEAEs to Monitor
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. TEAEs to monitor included anaphylaxis and hypersensitivity, cardiac dysfunction, diarrhoea Grade ≥3, pregnancy-related AEs, interstitial lung disease, infusion-/administration-related reactions, mucositis, (febrile) neutropenia, rash/skin reactions, and suspected transmission of infectious agent.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
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Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Age ≤65 Years Age >65 Years
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Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1167 269
Measure Type: Count of Participants
Unit of Measure: Participants
Any Serious TEAE
415
  35.6%
120
  44.6%
Any TEAE Leading to Death
17
   1.5%
14
   5.2%
Any TEAE - Grade 3 or Higher (≥3)
688
  59.0%
191
  71.0%
Any TEAE Related to Pertuzumab - Any Grade
845
  72.4%
192
  71.4%
Any Grade ≥3 TEAE Related to Pertuzumab
224
  19.2%
62
  23.0%
Any TEAE to Monitor - Any Grade
1081
  92.6%
239
  88.8%
14.Primary Outcome
Title Subgroup Analysis by Taxane Chemotherapy: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), TEAEs Leading to Death, Grade ≥3 TEAEs, Any-Grade and Grade ≥3 TEAEs Related to Pertuzumab, and TEAEs to Monitor
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. TEAEs to monitor included anaphylaxis and hypersensitivity, cardiac dysfunction, diarrhoea Grade ≥3, pregnancy-related AEs, interstitial lung disease, infusion-/administration-related reactions, mucositis, (febrile) neutropenia, rash/skin reactions, and suspected transmission of infectious agent.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
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Safety Population: all participants who received at least one dose of any study treatment. Only participants who received any taxane chemotherapy during the study were included in this analysis.
Arm/Group Title Docetaxel Paclitaxel Nab-Paclitaxel
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Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Participants in this subgroup received docetaxel as their taxane chemotherapy, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Participants in this subgroup received paclitaxel as their taxane chemotherapy, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Participants in this subgroup received nab-paclitaxel as their taxane chemotherapy, per the investigator's choice.
Overall Number of Participants Analyzed 775 588 65
Measure Type: Count of Participants
Unit of Measure: Participants
Any Serious TEAE
300
  38.7%
210
  35.7%
22
  33.8%
Any TEAE Leading to Death
14
   1.8%
16
   2.7%
1
   1.5%
Any TEAE - Grade 3 or Higher (≥3)
491
  63.4%
349
  59.4%
36
  55.4%
Any TEAE Related to Pertuzumab - Any Grade
547
  70.6%
434
  73.8%
52
  80.0%
Any Grade ≥3 TEAE Related to Pertuzumab
171
  22.1%
105
  17.9%
9
  13.8%
Any TEAE to Monitor - Any Grade
709
  91.5%
541
  92.0%
64
  98.5%
15.Primary Outcome
Title Subgroup Analysis by ECOG Performance Status at Baseline: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
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Safety Population: all participants who received at least one dose of any study treatment. There were 2 participants with missing evaluations for ECOG performance status at baseline who were excluded from this analysis.
Arm/Group Title ECOG Performance Status 0 or 1 ECOG Performance Status 2
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1371 63
Measure Type: Count of Participants
Unit of Measure: Participants
Any Serious TEAE
502
  36.6%
33
  52.4%
Any TEAE - Grade 3 or Higher (≥3)
837
  61.1%
41
  65.1%
Any Grade ≥3 TEAE Related to Pertuzumab
273
  19.9%
13
  20.6%
16.Primary Outcome
Title Subgroup Analysis by Visceral Disease at Baseline: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
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Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Visceral Disease Non-Visceral Disease
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Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 992 444
Measure Type: Count of Participants
Unit of Measure: Participants
Any Serious TEAE
353
  35.6%
182
  41.0%
Any TEAE - Grade 3 or Higher (≥3)
610
  61.5%
269
  60.6%
Any Grade ≥3 TEAE Related to Pertuzumab
197
  19.9%
89
  20.0%
17.Primary Outcome
Title Subgroup Analysis by Prior (Neo)Adjuvant Chemotherapy: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
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Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Prior (Neo)Adjuvant Chemotherapy No Prior (Neo)Adjuvant Chemotherapy
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Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 786 650
Measure Type: Count of Participants
Unit of Measure: Participants
Any Serious TEAE
283
  36.0%
252
  38.8%
Any TEAE - Grade 3 or Higher (≥3)
493
  62.7%
386
  59.4%
Any Grade ≥3 TEAE Related to Pertuzumab
169
  21.5%
117
  18.0%
18.Primary Outcome
Title Subgroup Analysis by Hormone Receptor Status at Baseline: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
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Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Hormone Receptor Positive Hormone Receptor Negative Hormone Receptor Status Unknown
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Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 918 512 6
Measure Type: Count of Participants
Unit of Measure: Participants
Any Serious TEAE
353
  38.5%
179
  35.0%
3
  50.0%
Any TEAE - Grade 3 or Higher (≥3)
573
  62.4%
303
  59.2%
3
  50.0%
Any Grade ≥3 TEAE Related to Pertuzumab
181
  19.7%
103
  20.1%
2
  33.3%
19.Primary Outcome
Title Subgroup Analysis by Previous Trastuzumab Therapy: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab
Hide Description Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE.
Time Frame From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Previous Trastuzumab Therapy No Previous Trastuzumab Therapy
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 400 1036
Measure Type: Count of Participants
Unit of Measure: Participants
Any Serious TEAE
135
  33.8%
400
  38.6%
Any TEAE - Grade 3 or Higher (≥3)
238
  59.5%
641
  61.9%
Any Grade ≥3 TEAE Related to Pertuzumab
77
  19.3%
209
  20.2%
20.Primary Outcome
Title Number of Participants With a Congestive Heart Failure Event
Hide Description Congestive heart failure was defined as the Standardised MedDRA Query (SMQ) 'Cardiac failure (wide)' from the Medical Dictionary for Regulatory Activities, version 22.1 (MedDRA version 22.1).
Time Frame From Baseline until 28 days after the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
478
  33.3%
21.Primary Outcome
Title Time to Onset of the First Episode of Congestive Heart Failure
Hide Description Congestive heart failure was defined as SMQ 'Cardiac failure (wide)' from the MedDRA version 22.1. Time to onset of the first episode of congestive heart failure was analyzed using a Kaplan-Meier approach. Participants who did not experience any congestive heart failure at the time of data-cut were censored at the date of the last attended visit whilst on-treatment (including visits up to and including 28 days after last dose of study treatment). Only treatment emergent congestive heart failure events are included.
Time Frame From Baseline until 28 days after the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(73.82 to NA)
[1]
The median and upper limit of the 95% confidence interval could not be calculated because not enough events had occurred during the study.
22.Primary Outcome
Title Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Values Over the Course of the Study
Hide Description All participants must have had a baseline LVEF ≥50% to enroll in the study; patients with significant cardiac disease or baseline LVEF below 50% were not eligible for this study. The change from baseline LVEF values were reported at every 3 cycles over the course of the study and at the final treatment, worst treatment, and maximum decrease values. The final treatment value was defined as the last LVEF value observed before all study treatment discontinuation. The worst treatment value was defined as the lowest LVEF value observed before all study treatment discontinuation. The maximum decrease value was defined as the largest decrease of LVEF value from baseline, or minimum increase if a participant's post-baseline LVEF measures were all larger than the baseline value.
Time Frame Baseline, predose on Day 1 of every 3 cycles (1 cycle is 3 weeks) during treatment period, and 28 days post-treatment safety follow-up. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Mean (Standard Deviation)
Unit of Measure: Percentage points of LVEF
Baseline (BL): Absolute Value at Visit Number Analyzed 1435 participants
64.6  (6.46)
Change from BL at Cycle 3 Number Analyzed 1311 participants
-1.1  (6.49)
Change from BL at Cycle 6 Number Analyzed 1248 participants
-1.5  (6.60)
Change from BL at Cycle 9 Number Analyzed 1150 participants
-2.1  (6.56)
Change from BL at Cycle 12 Number Analyzed 1028 participants
-1.9  (6.66)
Change from BL at Cycle 15 Number Analyzed 898 participants
-2.2  (6.50)
Change from BL at Cycle 18 Number Analyzed 816 participants
-1.8  (6.77)
Change from BL at Cycle 21 Number Analyzed 731 participants
-1.9  (6.79)
Change from BL at Cycle 24 Number Analyzed 681 participants
-1.9  (6.93)
Change from BL at Cycle 27 Number Analyzed 633 participants
-2.1  (6.81)
Change from BL at Cycle 30 Number Analyzed 589 participants
-1.8  (6.80)
Change from BL at Cycle 33 Number Analyzed 558 participants
-1.9  (6.97)
Change from BL at Cycle 36 Number Analyzed 509 participants
-2.1  (6.53)
Change from BL at Cycle 39 Number Analyzed 480 participants
-2.1  (6.77)
Change from BL at Cycle 42 Number Analyzed 451 participants
-1.9  (6.52)
Change from BL at Cycle 45 Number Analyzed 428 participants
-2.2  (6.94)
Change from BL at Cycle 48 Number Analyzed 390 participants
-2.1  (6.67)
Change from BL at Cycle 51 Number Analyzed 357 participants
-1.6  (6.75)
Change from BL at Cycle 54 Number Analyzed 325 participants
-1.7  (6.38)
Change from BL at Cycle 57 Number Analyzed 332 participants
-1.7  (6.87)
Change from BL at Cycle 60 Number Analyzed 313 participants
-1.5  (6.46)
Change from BL at Cycle 63 Number Analyzed 302 participants
-1.6  (7.13)
Change from BL at Cycle 66 Number Analyzed 284 participants
-2.0  (6.63)
Change from BL at Cycle 69 Number Analyzed 270 participants
-1.9  (6.45)
Change from BL at Cycle 72 Number Analyzed 259 participants
-2.1  (6.80)
Change from BL at Cycle 75 Number Analyzed 254 participants
-1.5  (6.84)
Change from BL at Cycle 78 Number Analyzed 245 participants
-1.8  (7.41)
Change from BL at Cycle 81 Number Analyzed 226 participants
-1.8  (6.98)
Change from BL at Cycle 84 Number Analyzed 215 participants
-1.6  (6.89)
Change from BL at Cycle 87 Number Analyzed 196 participants
-1.9  (6.31)
Change from BL at Cycle 90 Number Analyzed 177 participants
-1.1  (6.68)
Change from BL at Cycle 93 Number Analyzed 156 participants
-1.6  (6.78)
Change from BL at Cycle 96 Number Analyzed 128 participants
-1.8  (6.33)
Change from BL at Cycle 99 Number Analyzed 106 participants
-2.0  (7.20)
Change from BL at Cycle 102 Number Analyzed 82 participants
-2.5  (7.95)
Change from BL at Cycle 105 Number Analyzed 65 participants
-2.5  (6.86)
Change from BL at Cycle 108 Number Analyzed 49 participants
-1.8  (8.04)
Change from BL at Cycle 111 Number Analyzed 42 participants
-3.3  (7.47)
Change from BL at Cycle 114 Number Analyzed 23 participants
-1.1  (8.12)
Change from BL at Cycle 117 Number Analyzed 17 participants
-5.8  (7.48)
Change from BL at Cycle 120 Number Analyzed 7 participants
-8.6  (6.70)
Change from BL at Cycle 123 Number Analyzed 3 participants
-9.3  (3.51)
Change from BL at Cycle 126 Number Analyzed 1 participants
-9.0 [1]   (NA)
Change from BL at End of Treatment Number Analyzed 546 participants
-3.8  (8.34)
Change from BL at Day 28 of Follow-Up Number Analyzed 584 participants
-3.2  (8.19)
Change from BL: Final Treatment Value Number Analyzed 1360 participants
-2.0  (6.77)
Change from BL: Worst Treatment Value Number Analyzed 1360 participants
-7.1  (6.88)
Change from BL: Maximum Decrease Value Number Analyzed 1398 participants
-7.7  (7.45)
[1]
Standard deviation could not be calculated using data from a single participant.
23.Primary Outcome
Title Number of Participants by Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Categories Over the Course of the Study
Hide Description All participants must have had a baseline LVEF greater than or equal to (≥)50% to enroll in the study; patients with significant cardiac disease or baseline LVEF below 50% were not eligible for this study. The number of participants are reported according to four change from baseline in LVEF value categories over the course of the study: 1) an increase or decrease from baseline LVEF less than (<)10% points or no change in LVEF; 2) an absolute LVEF value <45% points and a decrease from baseline LVEF ≥10% points to <15% points; 3) an absolute LVEF value <45% points and a decrease from baseline LVEF ≥15% points; or 4) an absolute LVEF value ≥45% points and a decrease from baseline LVEF ≥10% points. BL = baseline; Decr. = decrease; Incr. = increase
Time Frame Baseline, predose on Day 1 of every 3 cycles (1 cycle is 3 weeks) during treatment period, and 28 days post-treatment safety follow-up. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Cycle 3 Number Analyzed 1311 participants
Incr. or Decr. from BL <10% Points, or No Change
1190
  90.8%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
2
   0.2%
LVEF<45% Points and Decr. from BL ≥15% Points
5
   0.4%
LVEF≥45% Points and Decr. from BL ≥10% Points
114
   8.7%
Cycle 6 Number Analyzed 1248 participants
Incr. or Decr. from BL <10% Points, or No Change
1110
  88.9%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
2
   0.2%
LVEF≥45% Points and Decr. from BL ≥10% Points
136
  10.9%
Cycle 9 Number Analyzed 1150 participants
Incr. or Decr. from BL <10% Points, or No Change
1005
  87.4%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
2
   0.2%
LVEF<45% Points and Decr. from BL ≥15% Points
4
   0.3%
LVEF≥45% Points and Decr. from BL ≥10% Points
139
  12.1%
Cycle 12 Number Analyzed 1028 participants
Incr. or Decr. from BL <10% Points, or No Change
906
  88.1%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
6
   0.6%
LVEF≥45% Points and Decr. from BL ≥10% Points
116
  11.3%
Cycle 15 Number Analyzed 898 participants
Incr. or Decr. from BL <10% Points, or No Change
780
  86.9%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
3
   0.3%
LVEF<45% Points and Decr. from BL ≥15% Points
6
   0.7%
LVEF≥45% Points and Decr. from BL ≥10% Points
109
  12.1%
Cycle 18 Number Analyzed 816 participants
Incr. or Decr. from BL <10% Points, or No Change
719
  88.1%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
5
   0.6%
LVEF≥45% Points and Decr. from BL ≥10% Points
92
  11.3%
Cycle 21 Number Analyzed 731 participants
Incr. or Decr. from BL <10% Points, or No Change
639
  87.4%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
4
   0.5%
LVEF≥45% Points and Decr. from BL ≥10% Points
88
  12.0%
Cycle 24 Number Analyzed 681 participants
Incr. or Decr. from BL <10% Points, or No Change
588
  86.3%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
2
   0.3%
LVEF≥45% Points and Decr. from BL ≥10% Points
91
  13.4%
Cycle 27 Number Analyzed 633 participants
Incr. or Decr. from BL <10% Points, or No Change
553
  87.4%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
2
   0.3%
LVEF≥45% Points and Decr. from BL ≥10% Points
78
  12.3%
Cycle 30 Number Analyzed 589 participants
Incr. or Decr. from BL <10% Points, or No Change
518
  87.9%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
1
   0.2%
LVEF≥45% Points and Decr. from BL ≥10% Points
70
  11.9%
Cycle 33 Number Analyzed 558 participants
Incr. or Decr. from BL <10% Points, or No Change
485
  86.9%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
1
   0.2%
LVEF≥45% Points and Decr. from BL ≥10% Points
72
  12.9%
Cycle 36 Number Analyzed 509 participants
Incr. or Decr. from BL <10% Points, or No Change
446
  87.6%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
1
   0.2%
LVEF≥45% Points and Decr. from BL ≥10% Points
62
  12.2%
Cycle 39 Number Analyzed 480 participants
Incr. or Decr. from BL <10% Points, or No Change
414
  86.3%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
1
   0.2%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
65
  13.5%
Cycle 42 Number Analyzed 451 participants
Incr. or Decr. from BL <10% Points, or No Change
405
  89.8%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
46
  10.2%
Cycle 45 Number Analyzed 428 participants
Incr. or Decr. from BL <10% Points, or No Change
358
  83.6%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
1
   0.2%
LVEF≥45% Points and Decr. from BL ≥10% Points
69
  16.1%
Cycle 48 Number Analyzed 390 participants
Incr. or Decr. from BL <10% Points, or No Change
340
  87.2%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
1
   0.3%
LVEF≥45% Points and Decr. from BL ≥10% Points
49
  12.6%
Cycle 51 Number Analyzed 357 participants
Incr. or Decr. from BL <10% Points, or No Change
314
  88.0%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
43
  12.0%
Cycle 54 Number Analyzed 325 participants
Incr. or Decr. from BL <10% Points, or No Change
292
  89.8%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
3
   0.9%
LVEF≥45% Points and Decr. from BL ≥10% Points
30
   9.2%
Cycle 57 Number Analyzed 332 participants
Incr. or Decr. from BL <10% Points, or No Change
291
  87.7%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
41
  12.3%
Cycle 60 Number Analyzed 313 participants
Incr. or Decr. from BL <10% Points, or No Change
284
  90.7%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
29
   9.3%
Cycle 63 Number Analyzed 302 participants
Incr. or Decr. from BL <10% Points, or No Change
263
  87.1%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
39
  12.9%
Cycle 66 Number Analyzed 284 participants
Incr. or Decr. from BL <10% Points, or No Change
249
  87.7%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
35
  12.3%
Cycle 69 Number Analyzed 270 participants
Incr. or Decr. from BL <10% Points, or No Change
237
  87.8%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
33
  12.2%
Cycle 72 Number Analyzed 259 participants
Incr. or Decr. from BL <10% Points, or No Change
224
  86.5%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
35
  13.5%
Cycle 75 Number Analyzed 254 participants
Incr. or Decr. from BL <10% Points, or No Change
224
  88.2%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
1
   0.4%
LVEF≥45% Points and Decr. from BL ≥10% Points
29
  11.4%
Cycle 78 Number Analyzed 245 participants
Incr. or Decr. from BL <10% Points, or No Change
214
  87.3%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
2
   0.8%
LVEF≥45% Points and Decr. from BL ≥10% Points
29
  11.8%
Cycle 81 Number Analyzed 226 participants
Incr. or Decr. from BL <10% Points, or No Change
196
  86.7%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
30
  13.3%
Cycle 84 Number Analyzed 215 participants
Incr. or Decr. from BL <10% Points, or No Change
192
  89.3%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
23
  10.7%
Cycle 87 Number Analyzed 196 participants
Incr. or Decr. from BL <10% Points, or No Change
174
  88.8%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
22
  11.2%
Cycle 90 Number Analyzed 177 participants
Incr. or Decr. from BL <10% Points, or No Change
161
  91.0%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
16
   9.0%
Cycle 93 Number Analyzed 156 participants
Incr. or Decr. from BL <10% Points, or No Change
140
  89.7%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
16
  10.3%
Cycle 96 Number Analyzed 128 participants
Incr. or Decr. from BL <10% Points, or No Change
115
  89.8%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
13
  10.2%
Cycle 99 Number Analyzed 106 participants
Incr. or Decr. from BL <10% Points, or No Change
92
  86.8%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
14
  13.2%
Cycle 102 Number Analyzed 82 participants
Incr. or Decr. from BL <10% Points, or No Change
68
  82.9%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
14
  17.1%
Cycle 105 Number Analyzed 65 participants
Incr. or Decr. from BL <10% Points, or No Change
56
  86.2%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
9
  13.8%
Cycle 108 Number Analyzed 49 participants
Incr. or Decr. from BL <10% Points, or No Change
41
  83.7%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
8
  16.3%
Cycle 111 Number Analyzed 42 participants
Incr. or Decr. from BL <10% Points, or No Change
34
  81.0%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
8
  19.0%
Cycle 114 Number Analyzed 23 participants
Incr. or Decr. from BL <10% Points, or No Change
19
  82.6%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
4
  17.4%
Cycle 117 Number Analyzed 17 participants
Incr. or Decr. from BL <10% Points, or No Change
11
  64.7%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
6
  35.3%
Cycle 120 Number Analyzed 7 participants
Incr. or Decr. from BL <10% Points, or No Change
4
  57.1%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
3
  42.9%
Cycle 123 Number Analyzed 3 participants
Incr. or Decr. from BL <10% Points, or No Change
2
  66.7%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
1
  33.3%
Cycle 126 Number Analyzed 1 participants
Incr. or Decr. from BL <10% Points, or No Change
1
 100.0%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
0
   0.0%
LVEF<45% Points and Decr. from BL ≥15% Points
0
   0.0%
LVEF≥45% Points and Decr. from BL ≥10% Points
0
   0.0%
End of Treatment Number Analyzed 546 participants
Incr. or Decr. from BL <10% Points, or No Change
431
  78.9%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
2
   0.4%
LVEF<45% Points and Decr. from BL ≥15% Points
26
   4.8%
LVEF≥45% Points and Decr. from BL ≥10% Points
87
  15.9%
Day 28 of Follow-Up Number Analyzed 584 participants
Incr. or Decr. from BL <10% Points, or No Change
472
  80.8%
LVEF<45% Points and Decr. from BL ≥10%-<15% Points
4
   0.7%
LVEF<45% Points and Decr. from BL ≥15% Points
22
   3.8%
LVEF≥45% Points and Decr. from BL ≥10% Points
86
  14.7%
24.Primary Outcome
Title Number of Participants With Laboratory Abnormalities in Hematology and Coagulation Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to NCI-CTC v4.0
Hide Description Clinical laboratory tests for hematology and coagulation parameters were performed at local laboratories. Laboratory toxicities were defined based on NCI-CTC v4.0 from Grades 1 (least severe) to 4 (most severe). Some laboratory parameters are bi-dimensional (i.e. can be graded in both the low and high direction). These parameters were split and presented in both directions. Baseline was defined as the last non-missing measurement taken prior to the first dose of study treatment (including unscheduled assessments). Values from all visits, including unscheduled visits, were included in the derivation of the worst post-baseline grade. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: was clinically significant (per investigator); was accompanied by clinical symptoms; resulted in a change in study treatment; or resulted in a medical intervention or a change in concomitant therapy.
Time Frame Predose at each treatment cycle (1 cycle is 3 weeks) from Baseline until 28 days after the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Absolute Neutrophil Count: Normal to Normal
844
  58.8%
Absolute Neutrophil Count: Normal to Grade 1
232
  16.2%
Absolute Neutrophil Count: Normal to Grade 2
169
  11.8%
Absolute Neutrophil Count: Normal to Grade 3
45
   3.1%
Absolute Neutrophil Count: Normal to Grade 4
27
   1.9%
Absolute Neutrophil Count: Normal to Missing
27
   1.9%
Absolute Neutrophil Count: Grade 1 to Normal
3
   0.2%
Absolute Neutrophil Count: Grade 1 to 1
11
   0.8%
Absolute Neutrophil Count: Grade 1 to 2
14
   1.0%
Absolute Neutrophil Count: Grade 1 to 3
3
   0.2%
Absolute Neutrophil Count: Grade 2 to 1
2
   0.1%
Absolute Neutrophil Count: Missing to Normal
21
   1.5%
Absolute Neutrophil Count: Missing to Grade 1
2
   0.1%
Absolute Neutrophil Count: Missing to Grade 2
3
   0.2%
Absolute Neutrophil Count: Missing to Grade 4
1
   0.1%
Absolute Neutrophil Count: Missing to Missing
32
   2.2%
Hemoglobin (High): Normal to Normal
1327
  92.4%
Hemoglobin (High): Normal to Grade 1
29
   2.0%
Hemoglobin (High): Normal to Grade 3
1
   0.1%
Hemoglobin (High): Normal to Missing
26
   1.8%
Hemoglobin (High): Grade 1 to Normal
28
   1.9%
Hemoglobin (High): Grade 1 to 1
5
   0.3%
Hemoglobin (High): Grade 1 to Missing
2
   0.1%
Hemoglobin (High): Grade 2 to Normal
1
   0.1%
Hemoglobin (High): Missing to Normal
14
   1.0%
Hemoglobin (High): Missing to Missing
3
   0.2%
Hemoglobin (Low): Normal to Normal
257
  17.9%
Hemoglobin (Low): Normal to Grade 1
648
  45.1%
Hemoglobin (Low): Normal to Grade 2
198
  13.8%
Hemoglobin (Low): Normal to Grade 3
10
   0.7%
Hemoglobin (Low): Normal to Missing
21
   1.5%
Hemoglobin (Low): Grade 1 to Normal
2
   0.1%
Hemoglobin (Low): Grade 1 to 1
109
   7.6%
Hemoglobin (Low): Grade 1 to 2
128
   8.9%
Hemoglobin (Low): Grade 1 to 3
12
   0.8%
Hemoglobin (Low): Grade 1 to Missing
4
   0.3%
Hemoglobin (Low): Grade 2 to 1
5
   0.3%
Hemoglobin (Low): Grade 2 to 2
18
   1.3%
Hemoglobin (Low): Grade 2 to 3
3
   0.2%
Hemoglobin (Low): Grade 2 to Missing
3
   0.2%
Hemoglobin (Low): Grade 3 to 1
1
   0.1%
Hemoglobin (Low): Missing to Normal
3
   0.2%
Hemoglobin (Low): Missing to Grade 1
7
   0.5%
Hemoglobin (Low): Missing to Grade 2
4
   0.3%
Hemoglobin (Low): Missing to Missing
3
   0.2%
Lymphocytes (High): Normal to Normal
1251
  87.1%
Lymphocytes (High): Normal to Grade 2
111
   7.7%
Lymphocytes (High): Normal to Grade 3
8
   0.6%
Lymphocytes (High): Normal to Missing
28
   1.9%
Lymphocytes (High): Grade 2 to Normal
4
   0.3%
Lymphocytes (High): Grade 2 to 2
10
   0.7%
Lymphocytes (High): Grade 2 to 3
2
   0.1%
Lymphocytes (High): Grade 3 to Normal
1
   0.1%
Lymphocytes (High): Grade 3 to 3
2
   0.1%
Lymphocytes (High): Missing to Normal
15
   1.0%
Lymphocytes (High): Missing to Grade 2
2
   0.1%
Lymphocytes (High): Missing to Missing
2
   0.1%
Lymphocytes (Low): Normal to Normal
565
  39.3%
Lymphocytes (Low): Normal to Grade 1
255
  17.8%
Lymphocytes (Low): Normal to Grade 2
210
  14.6%
Lymphocytes (Low): Normal to Grade 3
76
   5.3%
Lymphocytes (Low): Normal to Grade 4
18
   1.3%
Lymphocytes (Low): Normal to Missing
19
   1.3%
Lymphocytes (Low): Grade 1 to Normal
11
   0.8%
Lymphocytes (Low): Grade 1 to 1
54
   3.8%
Lymphocytes (Low): Grade 1 to 2
51
   3.6%
Lymphocytes (Low): Grade 1 to 3
18
   1.3%
Lymphocytes (Low): Grade 1 to 4
6
   0.4%
Lymphocytes (Low): Grade 1 to Missing
5
   0.3%
Lymphocytes (Low): Grade 2 to Normal
12
   0.8%
Lymphocytes (Low): Grade 2 to 1
8
   0.6%
Lymphocytes (Low): Grade 2 to 2
37
   2.6%
Lymphocytes (Low): Grade 2 to 3
19
   1.3%
Lymphocytes (Low): Grade 2 to 4
1
   0.1%
Lymphocytes (Low): Grade 2 to Missing
2
   0.1%
Lymphocytes (Low): Grade 3 to 1
3
   0.2%
Lymphocytes (Low): Grade 3 to 2
8
   0.6%
Lymphocytes (Low): Grade 3 to 3
14
   1.0%
Lymphocytes (Low): Grade 3 to 4
2
   0.1%
Lymphocytes (Low): Grade 3 to Missing
1
   0.1%
Lymphocytes (Low): Grade 4 to 2
1
   0.1%
Lymphocytes (Low): Grade 4 to 3
3
   0.2%
Lymphocytes (Low): Grade 4 to 4
16
   1.1%
Lymphocytes (Low): Grade 4 to Missing
1
   0.1%
Lymphocytes (Low): Missing to Normal
11
   0.8%
Lymphocytes (Low): Missing to Grade 1
3
   0.2%
Lymphocytes (Low): Missing to Grade 2
3
   0.2%
Lymphocytes (Low): Missing to Grade 3
1
   0.1%
Lymphocytes (Low): Missing to Missing
2
   0.1%
Platelet Count: Normal to Normal
1222
  85.1%
Platelet Count: Normal to Grade 1
149
  10.4%
Platelet Count: Normal to Grade 3
1
   0.1%
Platelet Count: Normal to Grade 4
2
   0.1%
Platelet Count: Normal to Missing
26
   1.8%
Platelet Count: Grade 1 to Normal
15
   1.0%
Platelet Count: Grade 1 to 1
16
   1.1%
Platelet Count: Grade 1 to 2
1
   0.1%
Platelet Count: Grade 1 to Missing
2
   0.1%
Platelet Count: Missing to Normal
1
   0.1%
Platelet Count: Missing to Grade 1
1
   0.1%
White Blood Cells (High): Normal to Normal
1391
  96.9%
White Blood Cells (High): Normal to Missing
29
   2.0%
White Blood Cells (High): Missing to Normal
14
   1.0%
White Blood Cells (High): Missing to Missing
2
   0.1%
White Blood Cells (Low): Normal to Normal
702
  48.9%
White Blood Cells (Low): Normal to Grade 1
392
  27.3%
White Blood Cells (Low): Normal to Grade 2
190
  13.2%
White Blood Cells (Low): Normal to Grade 3
29
   2.0%
White Blood Cells (Low): Normal to Grade 4
6
   0.4%
White Blood Cells (Low): Normal to Missing
29
   2.0%
White Blood Cells (Low): Grade 1 to Normal
4
   0.3%
White Blood Cells (Low): Grade 1 to 1
20
   1.4%
White Blood Cells (Low): Grade 1 to 2
33
   2.3%
White Blood Cells (Low): Grade 1 to 3
4
   0.3%
White Blood Cells (Low): Grade 2 to Normal
2
   0.1%
White Blood Cells (Low): Grade 2 to 1
4
   0.3%
White Blood Cells (Low): Grade 2 to 2
3
   0.2%
White Blood Cells (Low): Grade 3 to Normal
1
   0.1%
White Blood Cells (Low): Grade 3 to 3
1
   0.1%
White Blood Cells (Low): Missing to Normal
9
   0.6%
White Blood Cells (Low): Missing to Grade 1
3
   0.2%
White Blood Cells (Low): Missing to Grade 2
1
   0.1%
White Blood Cells (Low): Missing to Grade 3
1
   0.1%
White Blood Cells (Low): Missing to Missing
2
   0.1%
International Normalized Ratio: Normal to Normal
17
   1.2%
International Normalized Ratio: Normal to Grade 1
52
   3.6%
International Normalized Ratio: Normal to Grade 2
1
   0.1%
International Normalized Ratio: Normal to Missing
3
   0.2%
International Normalized Ratio: Grade 1 to Normal
1
   0.1%
International Normalized Ratio: Grade 2 to 3
1
   0.1%
International Normalized Ratio: Missing to Normal
424
  29.5%
International Normalized Ratio: Missing to Grade 1
615
  42.8%
International Normalized Ratio: Missing to Grade 2
23
   1.6%
International Normalized Ratio: Missing to Grade 3
14
   1.0%
International Normalized Ratio: Missing to Missing
285
  19.8%
25.Primary Outcome
Title Number of Participants With Laboratory Abnormalities in Hematology and Coagulation Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to Normal Range Criteria
Hide Description Clinical laboratory tests for hematology and coagulation parameters were performed at local laboratories. Laboratory toxicities were defined based on local laboratory normal ranges (for parameters with NCI-CTC grade not defined). Some laboratory parameters are bi-dimensional (i.e. can be graded in both the low and high direction). These parameters were split and presented in both directions. Baseline was defined as the last non-missing measurement taken prior to the first dose of study treatment (including unscheduled assessments). Values from all visits, including unscheduled visits, were included in the derivation of the worst post-baseline grade. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: was clinically significant (per investigator); was accompanied by clinical symptoms; resulted in a change in study treatment; or resulted in a medical intervention or a change in concomitant therapy.
Time Frame Predose at each treatment cycle (1 cycle is 3 weeks) from Baseline until 28 days after the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Basophils (High): Normal to Normal
1020
  71.0%
Basophils (High): Normal to Low
3
   0.2%
Basophils (High): Normal to High
261
  18.2%
Basophils (High): Low to Normal
16
   1.1%
Basophils (High): Low to Low
1
   0.1%
Basophils (High): Low to High
5
   0.3%
Basophils (High): High to Normal
11
   0.8%
Basophils (High): High to High
38
   2.6%
Basophils (High): Missing to Normal
21
   1.5%
Basophils (High): Missing to High
7
   0.5%
Basophils (High): Missing to Missing
53
   3.7%
Basophils (Low): Normal to Normal
1206
  84.0%
Basophils (Low): Normal to Low
77
   5.4%
Basophils (Low): Normal to High
1
   0.1%
Basophils (Low): Low to Normal
3
   0.2%
Basophils (Low): Low to Low
18
   1.3%
Basophils (Low): Low to Missing
1
   0.1%
Basophils (Low): High to Normal
36
   2.5%
Basophils (Low): High to Low
5
   0.3%
Basophils (Low): High to High
8
   0.6%
Basophils (Low): Missing to Normal
40
   2.8%
Basophils (Low): Missing to Low
3
   0.2%
Basophils (Low): Missing to High
1
   0.1%
Basophils (Low): Missing to Missing
37
   2.6%
Eosinophils (High): Normal to Normal
904
  63.0%
Eosinophils (High): Normal to Low
13
   0.9%
Eosinophils (High): Normal to High
283
  19.7%
Eosinophils (High): Low to Normal
66
   4.6%
Eosinophils (High): Low to Low
13
   0.9%
Eosinophils (High): Low to High
36
   2.5%
Eosinophils (High): High to Normal
11
   0.8%
Eosinophils (High): High to High
35
   2.4%
Eosinophils (High): Missing to Normal
17
   1.2%
Eosinophils (High): Missing to Low
1
   0.1%
Eosinophils (High): Missing to High
7
   0.5%
Eosinophils (High): Missing to Missing
50
   3.5%
Eosinophils (Low): Normal to Normal
810
  56.4%
Eosinophils (Low): Normal to Low
390
  27.2%
Eosinophils (Low): Low to Normal
13
   0.9%
Eosinophils (Low): Low to Low
101
   7.0%
Eosinophils (Low): Low to High
1
   0.1%
Eosinophils (Low): High to Normal
28
   1.9%
Eosinophils (Low): High to Low
13
   0.9%
Eosinophils (Low): High to High
5
   0.3%
Eosinophils (Low): Missing to Normal
37
   2.6%
Eosinophils (Low): Missing to Low
10
   0.7%
Eosinophils (Low): Missing to Missing
28
   1.9%
Hematocrit (High): Normal to Normal
953
  66.4%
Hematocrit (High): Normal to Low
47
   3.3%
Hematocrit (High): Normal to High
58
   4.0%
Hematocrit (High): Normal to Missing
4
   0.3%
Hematocrit (High): Low to Normal
201
  14.0%
Hematocrit (High): Low to Low
97
   6.8%
Hematocrit (High): Low to High
10
   0.7%
Hematocrit (High): Low to Missing
2
   0.1%
Hematocrit (High): High to Normal
17
   1.2%
Hematocrit (High): High to High
12
   0.8%
Hematocrit (High): Missing to Normal
15
   1.0%
Hematocrit (High): Missing to High
1
   0.1%
Hematocrit (High): Missing to Missing
19
   1.3%
Hematocrit (Low): Normal to Normal
223
  15.5%
Hematocrit (Low): Normal to Low
837
  58.3%
Hematocrit (Low): Normal to Missing
2
   0.1%
Hematocrit (Low): Low to Normal
5
   0.3%
Hematocrit (Low): Low to Low
305
  21.2%
Hematocrit (Low): High to Normal
13
   0.9%
Hematocrit (Low): High to Low
16
   1.1%
Hematocrit (Low): Missing to Normal
3
   0.2%
Hematocrit (Low): Missing to Low
12
   0.8%
Hematocrit (Low): Missing to Missing
20
   1.4%
Monocytes (High): Normal to Normal
802
  55.8%
Monocytes (High): Normal to Low
3
   0.2%
Monocytes (High): Normal to High
365
  25.4%
Monocytes (High): Low to Normal
58
   4.0%
Monocytes (High): Low to Low
6
   0.4%
Monocytes (High): Low to High
17
   1.2%
Monocytes (High): High to Normal
29
   2.0%
Monocytes (High): High to Low
1
   0.1%
Monocytes (High): High to High
82
   5.7%
Monocytes (High): Missing to Normal
12
   0.8%
Monocytes (High): Missing to High
8
   0.6%
Monocytes (High): Missing to Missing
53
   3.7%
Monocytes (Low): Normal to Normal
747
  52.0%
Monocytes (Low): Normal to Low
420
  29.2%
Monocytes (Low): Normal to High
3
   0.2%
Monocytes (Low): Low to Normal
11
   0.8%
Monocytes (Low): Low to Low
70
   4.9%
Monocytes (Low): High to Normal
64
   4.5%
Monocytes (Low): High to Low
40
   2.8%
Monocytes (Low): High to High
8
   0.6%
Monocytes (Low): Missing to Normal
13
   0.9%
Monocytes (Low): Missing to Low
10
   0.7%
Monocytes (Low): Missing to High
5
   0.3%
Monocytes (Low): Missing to Missing
45
   3.1%
Red Blood Cells (High): Normal to Normal
975
  67.9%
Red Blood Cells (High): Normal to Low
31
   2.2%
Red Blood Cells (High): Normal to High
111
   7.7%
Red Blood Cells (High): Low to Normal
131
   9.1%
Red Blood Cells (High): Low to Low
61
   4.2%
Red Blood Cells (High): Low to High
15
   1.0%
Red Blood Cells (High): High to Normal
22
   1.5%
Red Blood Cells (High): High to High
45
   3.1%
Red Blood Cells (High): Missing to Normal
18
   1.3%
Red Blood Cells (High): Missing to Low
2
   0.1%
Red Blood Cells (High): Missing to High
2
   0.1%
Red Blood Cells (High): Missing to Missing
23
   1.6%
Red Blood Cells (Low): Normal to Normal
350
  24.4%
Red Blood Cells (Low): Normal to Low
767
  53.4%
Red Blood Cells (Low): Low to Normal
10
   0.7%
Red Blood Cells (Low): Low to Low
197
  13.7%
Red Blood Cells (Low): High to Normal
44
   3.1%
Red Blood Cells (Low): High to Low
21
   1.5%
Red Blood Cells (Low): High to High
2
   0.1%
Red Blood Cells (Low): Missing to Normal
6
   0.4%
Red Blood Cells (Low): Missing to Low
16
   1.1%
Red Blood Cells (Low): Missing to Missing
23
   1.6%
PTT (High): Normal to Normal
46
   3.2%
PTT (High): Normal to Low
1
   0.1%
PTT (High): Normal to High
15
   1.0%
PTT (High): Low to Normal
19
   1.3%
PTT (High): Low to Low
1
   0.1%
PTT (High): Low to High
1
   0.1%
PTT (High): High to High
1
   0.1%
PTT (High): Missing to Normal
19
   1.3%
PTT (High): Missing to Low
5
   0.3%
PTT (High): Missing to High
9
   0.6%
PTT (High): Missing to Missing
1319
  91.9%
PTT (Low): Normal to Normal
46
   3.2%
PTT (Low): Normal to Low
16
   1.1%
PTT (Low): Low to Normal
3
   0.2%
PTT (Low): Low to Low
18
   1.3%
PTT (Low): High to Normal
1
   0.1%
PTT (Low): Missing to Normal
20
   1.4%
PTT (Low): Missing to Low
6
   0.4%
PTT (Low): Missing to High
5
   0.3%
PTT (Low): Missing to Missing
1321
  92.0%
26.Primary Outcome
Title Number of Participants With Laboratory Abnormalities in Biochemistry Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to NCI-CTC v4.0
Hide Description Clinical laboratory tests for biochemistry parameters were performed at local laboratories. Laboratory toxicities were defined based on NCI-CTC v4.0 from Grades 1 (least severe) to 4 (most severe). Some laboratory parameters are bi-dimensional (i.e. can be graded in both the low and high direction). These parameters were split and presented in both directions. Baseline was defined as the last non-missing measurement taken prior to the first dose of study treatment (including unscheduled assessments). Values from all visits, including unscheduled visits, were included in the derivation of the worst post-baseline grade. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: was clinically significant (per investigator); was accompanied by clinical symptoms; resulted in a change in study treatment; or resulted in a medical intervention or a change in concomitant therapy.
Time Frame Predose at each treatment cycle (1 cycle is 3 weeks) from Baseline until 28 days after the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of any study treatment.
Arm/Group Title Pertuzumab + Trastuzumab + Taxane
Hide Arm/Group Description:
Participants received pertuzumab and trastuzumab intravenously (IV) plus taxane chemotherapy once of every 3 weeks per treatment cycle until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurred first. Taxane chemotherapy was docetaxel, paclitaxel, or nab-paclitaxel, per the investigator's choice.
Overall Number of Participants Analyzed 1436
Measure Type: Count of Participants
Unit of Measure: Participants
Alanine Aminotransferase: Normal to Normal
610
  42.5%
Alanine Aminotransferase: Normal to Grade 1
425
  29.6%
Alanine Aminotransferase: Normal to Grade 2
26
   1.8%
Alanine Aminotransferase: Normal to Grade 3
19
   1.3%
Alanine Aminotransferase: Normal to Missing
25
   1.7%
Alanine Aminotransferase: Grade 1 to Normal
75
   5.2%
Alanine Aminotransferase: Grade 1 to 1
151
  10.5%
Alanine Aminotransferase: Grade 1 to 2
26
   1.8%
Alanine Aminotransferase: Grade 1 to 3
14
   1.0%
Alanine Aminotransferase: Grade 1 to Missing
6
   0.4%
Alanine Aminotransferase: Grade 2 to Normal
8
   0.6%
Alanine Aminotransferase: Grade 2 to 1
28
   1.9%
Alanine Aminotransferase: Grade 2 to 2
5
   0.3%
Alanine Aminotransferase: Grade 2 to 3
1
   0.1%
Alanine Aminotransferase: Grade 3 to 1
2
   0.1%
Alanine Aminotransferase: Missing to Normal
7
   0.5%
Alanine Aminotransferase: Missing to Grade 1
4
   0.3%
Alanine Aminotransferase: Missing to Grade 2
1
   0.1%
Alanine Aminotransferase: Missing to Missing
3
   0.2%
Aspartate Aminotransferase: Normal to Normal
562
  39.1%
Aspartate Aminotransferase: Normal to Grade 1
386
  26.9%
Aspartate Aminotransferase: Normal to Grade 2
22
   1.5%
Aspartate Aminotransferase: Normal to Grade 3
9
   0.6%
Aspartate Aminotransferase: Normal to Missing
15
   1.0%
Aspartate Aminotransferase: Grade 1 to Normal
120
   8.4%
Aspartate Aminotransferase: Grade 1 to 1
187
  13.0%
Aspartate Aminotransferase: Grade 1 to 2
24
   1.7%
Aspartate Aminotransferase: Grade 1 to 3
9
   0.6%
Aspartate Aminotransferase: Grade 1 to Missing
14
   1.0%
Aspartate Aminotransferase: Grade 2 to Normal
13
   0.9%
Aspartate Aminotransferase: Grade 2 to 1
29
   2.0%
Aspartate Aminotransferase: Grade 2 to 2
3
   0.2%
Aspartate Aminotransferase: Grade 2 to Missing
3
   0.2%
Aspartate Aminotransferase: Grade 3 to Normal
2
   0.1%
Aspartate Aminotransferase: Grade 3 to 1
7
   0.5%
Aspartate Aminotransferase: Grade 3 to Missing
1
   0.1%
Aspartate Aminotransferase: Missing to Normal
13
   0.9%
Aspartate Aminotransferase: Missing to Grade 1
9
   0.6%
Aspartate Aminotransferase: Missing to Grade 2
2
   0.1%
Aspartate Aminotransferase: Missing to Missing
6
   0.4%
Albumin: Normal to Normal
785
  54.7%
Albumin: Normal to Grade 1
357
  24.9%
Albumin: Normal to Grade 2
86
   6.0%
Albumin: Normal to Grade 3
10
   0.7%
Albumin: Normal to Missing
23
   1.6%
Albumin: Grade 1 to Normal
13
   0.9%
Albumin: Grade 1 to 1
43
   3.0%
Albumin: Grade 1 to 2
35
   2.4%
Albumin: Grade 1 to 3
1
   0.1%
Albumin: Grade 1 to Missing
7
   0.5%
Albumin: Grade 2 to Normal
3
   0.2%
Albumin: Grade 2 to 1
5
   0.3%
Albumin: Grade 2 to 2
8
   0.6%
Albumin: Grade 2 to 3
2
   0.1%
Albumin: Grade 2 to Missing
2
   0.1%
Albumin: Grade 3 to 2
1
   0.1%
Albumin: Grade 3 to Missing
1
   0.1%
Albumin: Missing to Normal
28
   1.9%
Albumin: Missing to Grade 1
14
   1.0%
Albumin: Missing to Grade 2
6
   0.4%
Albumin: Missing to Missing
6
   0.4%
Alkaline Phosphatase: Normal to Normal
605
  42.1%
Alkaline Phosphatase: Normal to Grade 1
329
  22.9%
Alkaline Phosphatase: Normal to Grade 2
14
   1.0%
Alkaline Phosphatase: Normal to Grade 3
2
   0.1%
Alkaline Phosphatase: Normal to Missing
18
   1.3%
Alkaline Phosphatase: Grade 1 to Normal
44
   3.1%
Alkaline Phosphatase: Grade 1 to 1
241
  16.8%
Alkaline Phosphatase: Grade 1 to 2
72
   5.0%
Alkaline Phosphatase: Grade 1 to 3
15
   1.0%
Alkaline Phosphatase: Grade 1 to Missing
6
   0.4%
Alkaline Phosphatase: Grade 2 to Normal
2
   0.1%
Alkaline Phosphatase: Grade 2 to 1
21
   1.5%
Alkaline Phosphatase: Grade 2 to 2
24
   1.7%
Alkaline Phosphatase: Grade 2 to 3
14
   1.0%
Alkaline Phosphatase: Grade 2 to Missing
8
   0.6%
Alkaline Phosphatase: Grade 3 to 1
2
   0.1%
Alkaline Phosphatase: Grade 3 to 2
1
   0.1%
Alkaline Phosphatase: Grade 3 to 3
4
   0.3%
Alkaline Phosphatase: Missing to Normal
7
   0.5%
Alkaline Phosphatase: Missing to Grade 1
3
   0.2%
Alkaline Phosphatase: Missing to Grade 3
1
   0.1%
Alkaline Phosphatase: Missing to Missing
3
   0.2%
Calcium (High): Normal to Normal
1060
  73.8%
Calcium (High): Normal to Grade 1
192
  13.4%
Calcium (High): Normal to Grade 2
2
   0.1%
Calcium (High): Normal to Grade 3
1
   0.1%
Calcium (High): Normal to Grade 4
1
   0.1%
Calcium (High): Normal to Missing
26
   1.8%
Calcium (High): Grade 1 to Normal
47
   3.3%
Calcium (High): Grade 1 to 1
47
   3.3%
Calcium (High): Grade 1 to 2
1
   0.1%
Calcium (High): Grade 1 to 3
1
   0.1%
Calcium (High): Grade 1 to Missing
5
   0.3%
Calcium (High): Grade 2 to Normal
1
   0.1%
Calcium (High): Grade 2 to 1
1
   0.1%
Calcium (High): Grade 2 to 2
1
   0.1%
Calcium (High): Grade 3 to Normal
2
   0.1%
Calcium (High): Grade 3 to 1
1
   0.1%
Calcium (High): Grade 3 to 2
1
   0.1%
Calcium (High): Grade 4 to Normal
1
   0.1%
Calcium (High): Missing to Normal
32
   2.2%
Calcium (High): Missing to Grade 1
3
   0.2%
Calcium (High): Missing to Missing
10
   0.7%
Calcium (Low): Normal to Normal
786
  54.7%
Calcium (Low): Normal to Grade 1
378
  26.3%
Calcium (Low): Normal to Grade 2
117
   8.1%
Calcium (Low): Normal to Grade 3
18
   1.3%
Calcium (Low): Normal to Missing
30
   2.1%
Calcium (Low): Grade 1 to Normal
5
   0.3%
Calcium (Low): Grade 1 to 1
31
   2.2%
Calcium (Low): Grade 1 to 2
12
   0.8%
Calcium (Low): Grade 1 to 3
2
   0.1%
Calcium (Low): Grade 1 to Missing
1
   0.1%
Calcium (Low): Grade 2 to Normal
5
   0.3%
Calcium (Low): Grade 2 to 1
1
   0.1%
Calcium (Low): Grade 2 to 2
4
   0.3%
Calcium (Low): Grade 3 to 3
1
   0.1%
Calcium (Low): Missing to Normal
20
   1.4%
Calcium (Low): Missing to Grade 1
11
   0.8%
Calcium (Low): Missing to Grade 2
4
   0.3%
Calcium (Low): Missing to Missing
10
   0.7%
Creatinine: Normal to Normal
176
  12.3%
Creatinine: Normal to Grade 1
960
  66.9%
Creatinine: Normal to Grade 2
175
  12.2%
Creatinine: Normal to Grade 3
5
   0.3%
Creatinine: Normal to Grade 4
5
   0.3%
Creatinine: Normal to Missing
26
   1.8%
Creatinine: Grade 1 to Normal
12
   0.8%
Creatinine: Grade 1 to 1
38
   2.6%
Creatinine: Grade 1 to 2
8
   0.6%
Creatinine: Grade 1 to Missing
3
   0.2%
Creatinine: Grade 2 to 2
3
   0.2%
Creatinine: Grade 2 to 3
1
   0.1%
Creatinine: Grade 2 to Missing
1
   0.1%
Creatinine: Missing to Normal
11
   0.8%
Creatinine: Missing to Grade 1
6
   0.4%
Creatinine: Missing to Missing
6
   0.4%
Gamma-Glutamyl Transpeptidase: Normal to Normal
498
  34.7%
Gamma-Glutamyl Transpeptidase: Normal to Grade 1
227
  15.8%
Gamma-Glutamyl Transpeptidase: Normal to Grade 2
39
   2.7%
Gamma-Glutamyl Transpeptidase: Normal to Grade 3
15
   1.0%
Gamma-Glutamyl Transpeptidase: Normal to Missing
12
   0.8%
Gamma-Glutamyl Transpeptidase: Grade 1 to Normal
64
   4.5%
Gamma-Glutamyl Transpeptidase: Grade 1 to 1
187
  13.0%
Gamma-Glutamyl Transpeptidase: Grade 1 to 2
75
   5.2%
Gamma-Glutamyl Transpeptidase: Grade 1 to 3
20
   1.4%
Gamma-Glutamyl Transpeptidase: Grade 1 to Missing
7
   0.5%
Gamma-Glutamyl Transpeptidase: Grade 2 to Normal
5
   0.3%
Gamma-Glutamyl Transpeptidase: Grade 2 to 1
52
   3.6%
Gamma-Glutamyl Transpeptidase: Grade 2 to 2
45
   3.1%
Gamma-Glutamyl Transpeptidase: Grade 2 to 3
21
   1.5%
Gamma-Glutamyl Transpeptidase: Grade 2 to Missing
5
   0.3%
Gamma-Glutamyl Transpeptidase: Grade 3 to Normal
2
   0.1%
Gamma-Glutamyl Transpeptidase: Grade 3 to 1
15
   1.0%
Gamma-Glutamyl Transpeptidase: Grade 3 to 2
38
   2.6%
Gamma-Glutamyl Transpeptidase: Grade 3 to 3
47
   3.3%
Gamma-Glutamyl Transpeptidase: Grade 3 to Missing
4
   0.3%
Gamma-Glutamyl Transpeptidase: Missing to Normal
14
   1.0%
Gamma-Glutamyl Transpeptidase: Missing to Grade 1
7
   0.5%
Gamma-Glutamyl Transpeptidase: Missing to Grade 2
10