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)

• 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: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This multicenter, open-label, single-arm, Phase IIIb study will evaluate the safety and tolerability of pertuzumab in combination with trastuzumab (Herceptin) and a taxane (docetaxel, paclitaxel or nab-paclitaxel) in first-line treatment in participants with metastatic or locally recurrent HER2-positive breast cancer. Participants will receive pertuzumab intravenously (IV) and trastuzumab (Herceptin) IV plus a taxane in cycles of 3 weeks each until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurs first.

Condition or disease	Intervention/treatment	Phase
Breast Neoplasms	Drug: Docetaxel; Drug: Nab-paclitaxel; Drug: Paclitaxel; Drug: Pertuzumab; Drug: Trastuzumab	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1436 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-Label, Single-Arm Study of Pertuzumab in Combination With Trastuzumab and a Taxane in First Line Treatment of Patients With HER2-Positive Advanced (Metastatic or Locally Recurrent) Breast Cancer
• Actual Study Start Date: June 1, 2012
• Actual Primary Completion Date: September 20, 2019
• Actual Study Completion Date: September 20, 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: Pertuzumab + Trastuzumab + Taxane; Participants will receive pertuzumab and trastuzumab (Herceptin) IV plus a taxane in cycles of 3 weeks each until predefined study end, unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurs first. Taxane chemotherapy can be either docetaxel, paclitaxel or nab-paclitaxel as per investigator's choice.

Drug: Docetaxel; Participants may receive 'docetaxel' taxane chemotherapy as per investigator's choice, administered in line with the respective product information and/or recognized clinical practice guidelines.; Drug: Nab-paclitaxel; Participants may receive 'nab-paclitaxel' taxane chemotherapy as per investigator's choice, administered in line with the respective product information and/or recognized clinical practice guidelines.; Drug: Paclitaxel; Participants may receive 'paclitaxel' taxane chemotherapy as per investigator's choice, administered in line with the respective product information and/or recognized clinical practice guidelines.; Drug: Pertuzumab; Participants will receive pertuzumab 840 milligrams (mg) IV on Day 1 or Day 2 of Cycle 1, followed by 420 mg IV on Day 1 or Day 2 of each subsequent 3-week cycle.; Other Name: RO 43-68451; Drug: Trastuzumab; Participants will receive trastuzumab (Herceptin) 8 milligrams per kilogram (mg/kg) IV on Day 1 or Day 2 of Cycle 1, followed by 6 mg/kg IV on Day 1 or Day 2 of each subsequent 3-week cycle, administered in line with the respective product Information and/or recognized clinical practice guidelines.; Other Name: Herceptin

Outcome Measures

Primary Outcome Measures :

1. 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) [ 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. ]
   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.
2. 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) [ Time Frame: The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
   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
3. 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) [ Time Frame: The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
   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
4. Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events, Occurring in ≥1% of Participants by System Organ Class and Preferred Term [ 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. ]
   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.
5. 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 [ 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. ]
   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.
6. 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 [ 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. ]
   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.
7. 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 [ 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. ]
   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
8. 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 [ 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. ]
   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
9. Number of Participants With Treatment-Emergent Adverse Events to Monitor of Any Grade, Occurring in ≥5% of Participants by 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. ]
   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.
10. Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events to Monitor, Occurring in ≥0.5% of Participants by Category and Preferred Term [ 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. ]
    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.
11. Number of Participants With Treatment-Emergent Adverse Events of Special Interest by Category and Preferred Term [ 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. ]
    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.
12. 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 [ 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. ]
    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.
13. 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 [ 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. ]
    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.
14. 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 [ 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. ]
    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.
15. 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 [ 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. ]
    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.
16. 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 [ 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. ]
    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.
17. 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 [ 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. ]
    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.
18. 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 [ 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. ]
    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.
19. 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 [ 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. ]
    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.
20. Number of Participants With a Congestive Heart Failure Event [ 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. ]
    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).
21. Time to Onset of the First Episode of Congestive Heart Failure [ 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. ]
    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.
22. Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Values Over the Course of the Study [ 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. ]
    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.
23. Number of Participants by Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Categories Over the Course of the Study [ 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. ]
    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
24. 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 [ 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. ]
    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.
25. 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 [ 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. ]
    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.
26. Number of Participants With Laboratory Abnormalities in Biochemistry Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to NCI-CTC v4.0 [ 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. ]
    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.
27. Number of Participants With Laboratory Abnormalities in Biochemistry Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to Normal Range Criteria [ 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. ]
    Clinical laboratory tests for biochemistry 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.

Secondary Outcome Measures :

1. Progression-Free Survival, as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) [ Time Frame: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
   Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression.
2. Subgroup Analysis by Region of Enrollment: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
   Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression.
3. Subgroup Analysis by Age (≤65 vs. >65 Years): Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
   Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression.
4. Subgroup Analysis by ECOG Performance Status at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
   Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression.
5. Subgroup Analysis by Taxane Chemotherapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
   Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression.
6. Subgroup Analysis by Visceral Disease at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
   Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression.
7. Subgroup Analysis by Prior (Neo)Adjuvant Chemotherapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
   Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression.
8. Subgroup Analysis by Hormone Receptor Status at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
   Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression.
9. Subgroup Analysis by Previous Trastuzumab Therapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
   Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression.
10. Overall Survival [ Time Frame: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation.
11. Subgroup Analysis by Region of Enrollment: Overall Survival [ Time Frame: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation.
12. Subgroup Analysis by Age (≤65 vs. >65 Years): Overall Survival [ Time Frame: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation.
13. Subgroup Analysis by ECOG Performance Status at Baseline: Overall Survival [ Time Frame: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation.
14. Subgroup Analysis by Taxane Chemotherapy: Overall Survival [ Time Frame: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation.
15. Subgroup Analysis by Visceral Disease at Baseline: Overall Survival [ Time Frame: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation.
16. Subgroup Analysis by Prior (Neo)Adjuvant Chemotherapy: Overall Survival [ Time Frame: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation.
17. Subgroup Analysis by Hormone Receptor Status at Baseline: Overall Survival [ Time Frame: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation.
18. Subgroup Analysis by Previous Trastuzumab Therapy: Overall Survival [ Time Frame: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation.
19. Overall Response Rate (Complete Response or Partial Response) Based on Best Overall Response (Confirmed) as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: Assessed every 3 cycles (1 cycle is 3 weeks) up to 36 months, and at least every 12 cycles thereafter, until disease progression or death. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    The overall response rate was defined as the percentage of participants with complete response (CR) or partial response (PR) as their best confirmed response (≥4 weeks later), as assessed by the investigator using RECIST v1.1 from the start of study treatment until disease progression/recurrence or death. Responses according to RECIST v1.1 are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimetres (mm).; PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants without post-baseline tumor assessments were considered non-responders.
20. Percentage of Participants by Best Overall Response as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: Assessed every 3 cycles (1 cycle is 3 weeks) up to 36 months, and at least every 12 cycles thereafter, until disease progression or death. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    Best overall response (BOR) was defined as the best response recorded from the first dose of study treatment until disease progression/recurrence or death in the absence of disease progression. The hierarchy used to determine BOR: Complete Response (CR)>Partial Response (PR)>Stable Disease (SD)>Progressive Disease (PD)>Not Evaluable. Note that CR or PR was confirmed ≥4 weeks later. RECIST v1.1 responses are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10 millimetres (mm).; PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum.; PD = At least 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study, and absolute increase of ≥5 mm.; SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
21. Subgroup Analysis by Age (≤65 vs. >65 Years): Overall Response Rate (Complete Response or Partial Response) Based on Best Overall Response (Confirmed) as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: Assessed every 3 cycles (1 cycle is 3 weeks) up to 36 months, and at least every 12 cycles thereafter, until disease progression or death. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    The overall response rate was defined as the percentage of participants with complete response (CR) or partial response (PR) as their best confirmed response (≥4 weeks later), as assessed by the investigator using RECIST v1.1 from the start of study treatment until disease progression/recurrence or death. Responses according to RECIST v1.1 are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimetres (mm).; PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants without post-baseline tumor assessments were considered non-responders.
22. Subgroup Analysis by Taxane Chemotherapy: Overall Response Rate (Complete Response or Partial Response) Based on Best Overall Response (Confirmed) as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: Assessed every 3 cycles (1 cycle is 3 weeks) up to 36 months, and at least every 12 cycles thereafter, until disease progression or death. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    The overall response rate was defined as the percentage of participants with complete response (CR) or partial response (PR) as their best confirmed response (≥4 weeks later), as assessed by the investigator using RECIST v1.1 from the start of study treatment until disease progression/recurrence or death. Responses according to RECIST v1.1 are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimetres (mm).; PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants without post-baseline tumor assessments were considered non-responders.
23. Clinical Benefit Rate (CR or PR, or SD for at Least 6 Months) Based on Best Overall Response as Assessed by the Investigator Using RECIST v.1.1 [ Time Frame: Assessed every 3 cycles (1 cycle is 3 weeks) up to 36 months, and at least every 12 cycles thereafter, until disease progression. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    The clinical benefit rate was defined as the percentage of participants whose best confirmed response (≥4 weeks later) was a complete response (CR) or partial response (PR), or stable disease (SD) that lasted at least 6 months, as assessed by the investigator using RECIST v1.1 from the start of study treatment until disease progression/recurrence or death. Clinical benefit responses according to RECIST v1.1 are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimetres (mm).; PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.; SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least 20% increase in sum of diameters of target lesions and absolute increase of ≥5 mm), taking as reference the smallest sum diameters while on study.
24. Duration of Response as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: From date of first confirmed response (CR or PR) to first documented disease progression or death from any cause, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    Duration of response (DOR) was defined as the time from when a confirmed best overall response of complete response (CR) or partial response (PR) was first documented to first documented disease progression or death from any cause (whichever occurred first). DOR was analyzed using a Kaplan-Meier approach. Participants who had not progressed or died after having had a confirmed response were censored at the date of their last tumor measurement. Response was assessed every 3 cycles (1 cycle is 3 weeks) up to 36 months, and at least every 12 cycles thereafter until event occurrence or end of study. Responses according to RECIST v1.1 are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimetres (mm).; PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
25. Time to Response for Participants With Best Overall Response of Complete Response or Partial Response, as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: From date of first study treatment until date of first confirmed response (CR or PR). The median (full range) duration of follow-up was 68.73 (0.03-87.29) months. ]
    Time to response (TTR) was defined as the time from the first study treatment administration to the date of first confirmed response (CR or PR). TTR was analyzed using a Kaplan-Meier approach. Participants who did not have CR or PR were censored at the date of their last evaluable tumor assessment. Participants for whom no post-baseline tumor assessments were available were censored at Day 1. Responses according to RECIST v1.1 are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimetres (mm).; PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
26. Change From Baseline in Functional Assessment of Cancer Therapy - Breast Cancer (FACT-B) Questionnaire Total Score Over the Course of the Study [ Time Frame: Baseline, 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. ]
    The FACT-B questionnaire (version 4) was administered only to female participants to assess quality of life in five subscales: physical, social, emotional, and functional well-being, and breast cancer. Participants were given a series of statements in each subscale and were asked to rate how true each statement was for them during the past 7 days on a 5-point scale ranging from 0 (not at all) to 4 (very much). The calculated FACT-B total score, ranging from 0 to 148, was the sum of the scores for each subscale, provided that at least 80% of the items had been answered; a higher score indicated a better quality of life. If any of the 5 subscale scores were missing, the total score was also set to missing. Baseline was defined as the last non-missing measurement taken prior to first dose of study treatment (including unscheduled assessments). Post-baseline values were summarized for planned visits only.
27. Change From Baseline in FACT-B Questionnaire Physical Well-Being Subscale Score Over the Course of the Study [ Time Frame: Baseline, 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. ]
    The FACT-B questionnaire (version 4) was administered only to female participants to assess quality of life in five subscales: physical, social, emotional, and functional well-being, and breast cancer. For the physical well-being subscale, participants were given a series of 7 statements and were asked to rate how true each statement was for them during the past 7 days on a 5-point scale ranging from 0 (not at all) to 4 (very much). The calculated FACT-B physical well-being subscale score, ranging from 0 to 28, was the sum of the scores for each statement only if at least 50% of items had been answered; the higher the score, the better the quality of life. Baseline was defined as the last non-missing measurement taken prior to first dose of study treatment (including unscheduled assessments). Post-baseline values were summarized for planned visits only.
28. Change From Baseline in FACT-B Questionnaire Social Well-Being Subscale Score Over the Course of the Study [ Time Frame: Baseline, 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. ]
    The FACT-B questionnaire (version 4) was administered only to female participants to assess quality of life in five subscales: physical, social, emotional, and functional well-being, and breast cancer. For the social well-being subscale, participants were given a series of 7 statements and were asked to rate how true each statement was for them during the past 7 days on a 5-point scale ranging from 0 (not at all) to 4 (very much). The calculated FACT-B social well-being subscale score, ranging from 0 to 28, was the sum of the scores for each statement only if at least 50% of items had been answered; the higher the score, the better the quality of life. Baseline was defined as the last non-missing measurement taken prior to first dose of study treatment (including unscheduled assessments). Post-baseline values were summarized for planned visits only.
29. Change From Baseline in FACT-B Questionnaire Emotional Well-Being Subscale Score Over the Course of the Study [ Time Frame: Baseline, 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. ]
    The FACT-B questionnaire (version 4) was administered only to female participants to assess quality of life in five subscales: physical, social, emotional, and functional well-being, and breast cancer. For the emotional well-being subscale, participants were given a series of 6 statements and were asked to rate how true each statement was for them during the past 7 days on a 5-point scale ranging from 0 (not at all) to 4 (very much). The calculated FACT-B emotional well-being subscale score, ranging from 0 to 24, was the sum of the scores for each statement only if at least 50% of items had been answered; the higher the score, the better the quality of life. Baseline was defined as the last non-missing measurement taken prior to first dose of study treatment (including unscheduled assessments). Post-baseline values were summarized for planned visits only.
30. Change From Baseline in FACT-B Questionnaire Functional Well-Being Subscale Score Over the Course of the Study [ Time Frame: Baseline, 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. ]
    The FACT-B questionnaire (version 4) was administered only to female participants to assess quality of life in five subscales: physical, social, emotional, and functional well-being, and breast cancer. For the functional well-being subscale, participants were given a series of 7 statements and were asked to rate how true each statement was for them during the past 7 days on a 5-point scale ranging from 0 (not at all) to 4 (very much). The calculated FACT-B functional well-being subscale score, ranging from 0 to 28, was the sum of the scores for each statement only if at least 50% of items had been answered; the higher the score, the better the quality of life. Baseline was defined as the last non-missing measurement taken prior to first dose of study treatment (including unscheduled assessments). Post-baseline values were summarized for planned visits only.
31. Change From Baseline in FACT-B Questionnaire Breast Cancer Subscale Score Over the Course of the Study [ Time Frame: Baseline, 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. ]
    The FACT-B questionnaire (version 4) was administered only to female participants to assess quality of life in five subscales: physical, social, emotional, and functional well-being, and breast cancer. For the breast cancer subscale, participants were given a series of 10 statements and were asked to rate how true each statement was for them during the past 7 days on a 5-point scale ranging from 0 (not at all) to 4 (very much). The calculated FACT-B breast cancer subscale score, ranging from 0 to 40, was the sum of the scores for each statement only if at least 50% of items had been answered; the higher the score, the better the quality of life. Baseline was defined as the last non-missing measurement taken prior to first dose of study treatment (including unscheduled assessments). Post-baseline values were summarized for planned visits only.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative resection
• HER2-positive breast cancer
• Eastern cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• LVEF of at least 50 percent (%)

Exclusion Criteria:

• Previous systemic non-hormonal anti-cancer therapy for metastatic or locally recurrent disease
• Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence less than or equal to (</=) 6 months
• Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except for trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting
• Disease progression while receiving trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting
• History of persistent Grade 2 or higher (National Cancer Institute Common Toxicity Criteria [NCI-CTC], Version 4.0) hematological toxicity resulting from previous adjuvant or neoadjuvant therapy
• Central nervous system (CNS) metastases
• Current peripheral neuropathy of Grade 3 or greater (NCI-CTC, version 4.0)
• History of other malignancy within the last 5 years prior to first study drug administration, except for carcinoma in situ of the cervix or basal cell carcinoma
• Inadequate bone marrow, liver or renal function
• Uncontrolled hypertension
• Hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection

Contacts and Locations

Locations

Algeria

CPMC; Service d'Oncologie Médicale

Algiers, Algeria, 16000

Argentina

Centro Oncologico Riojano Integral (CORI)

La Rioja, Argentina, F5300COE

Instituto de Oncología de Rosario

Rosario, Argentina, S2000KZE

Australia, Australian Capital Territory

Canberra Hospital; Medical Oncology

Canberra, Australian Capital Territory, Australia, 2606

Australia, New South Wales

Royal Prince Alfred Hospital; Medical Oncology

Camperdown, New South Wales, Australia, 2050

Australia, Queensland

HOCA Chermside

Chermside, Queensland, Australia, 4032

Mater Hospital; Cancer Services

South Brisbane, Queensland, Australia, 4101

Australia, Victoria

Austin and Repatriation Medical Centre; Cancer Services

Melbourne, Victoria, Australia, 3084

Royal Melbourne Hospital; Hematology and Medical Oncology

Parkville, Victoria, Australia, 3052

Austria

Lkh-Univ. Klinikum Graz; Klinik Für Gynäkologie

Graz, Austria, 8036

LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie

Graz, Austria, 8036

Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie

Innsbruck, Austria, 6020

Ordensklinikum Linz Barmherzige Schwestern; Abt. fur Innere Medizin 1

Linz, Austria, 4010

Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.

Salzburg, Austria, 5020

A.Ö. Lhk; Ii. Medizinische Abt. Mit Schwerpunkt Gaströnter. & Onkologie

Steyr, Austria, 4400

Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie

Wien, Austria, 1090

Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie

Wien, Austria, 1090

Belgium

UZ Brussel

Brussel, Belgium, 1090

UZ Antwerpen

Edegem, Belgium, 2650

UZ Gent

Gent, Belgium, 9000

UZ Leuven Gasthuisberg

Leuven, Belgium, 3000

CHU Sart-Tilman

Liège, Belgium, 4000

Brazil

Oncologistas Associados

Rio de Janeiro, RJ, Brazil, 22271-110

Hospital Sao Lucas - PUCRS

Porto Alegre, RS, Brazil, 90610-000

Hospital Amaral Carvalho

Jau, SP, Brazil, 17210-120

Hospital Sirio Libanes; Centro de Oncologia

Sao Paulo, SP, Brazil, 01308-050

Hospital Perola Byington

Sao Paulo, SP, Brazil, 01317-000

Hospital das Clinicas - FMUSP

Sao Paulo, SP, Brazil, 05403-000

Hospital Sao Jose

São Paulo, SP, Brazil, CEP 01321-001

Canada, Alberta

Cross Cancer Institute ; Dept of Medical Oncology

Edmonton, Alberta, Canada, T6G 1Z2

Canada, British Columbia

Lions Gate Hospital

North Vancouver, British Columbia, Canada, V7L 2L7

Bcca - Vancouver Island Cancer Centre; Oncology

Victoria, British Columbia, Canada, V8R 6V5

Canada, Nova Scotia

Queen Elizabeth II Health Sciences Centre; Oncology

Halifax, Nova Scotia, Canada, B3H 2Y9

Canada, Ontario

William Osler Health System Brampton Civic Hospital

Brampton, Ontario, Canada, L6R 3J7

Grand River Hospital

Kitchener, Ontario, Canada, N2G 1G3

Sunnybrook Odette Cancer Centre

Toronto, Ontario, Canada, M4N 3M5

Canada, Quebec

CSSS champlain - Charles-Le Moyne

Greenfield Park, Quebec, Canada, J4V 2H1

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada, H2X 0C2

McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology

Montreal, Quebec, Canada, H3T 1E2

China

Beijing Cancer Hospital

Beijing, China, 100142

Southwest Hospital , Third Military Medical University

Chongqing, China, 400038

Sun Yet-sen University Cancer Center

Guangzhou, China, 510060

Heilongjiang Provincial Tumor Hospital

Harbin, China, 150040

Jiangsu Cancer Hospital

Nanjing, China, 210009

Fudan University Shanghai Cancer Center

Shanghai, China, 200120

Tianjin Cancer Hospital

Tianjin, China, 300060

The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)

Xi'an, China, 710032

First Affiliated Hospital of Medical College of Xi'an Jiaotong University

Xi'an, China, 710061

Ecuador

Hospital Solca Portoviejo; Oncologia

Portoviejo, Ecuador, EC130104

Hospital Solca Quito; Oncologia

Quito, Ecuador, EC170124

Egypt

Manial Specialized Hospital; Oncology

Cairo, Egypt, 11555

El Mokatam HIO Hospital

Cairo, Egypt, 11654

Nci; Oncology Dept

Cairo, Egypt, 11796

Estonia

North Estonia Medical Centre Foundation; Oncology Center

Tallinn, Estonia, 13419

Tartu University Hospital; Clinic of Hematology and Oncology

Tartu, Estonia, 50406

Finland

Helsinki University Central Hospital; Oncology Clinics

Helsinki, Finland, 00029

Satakunta Central Hospital; Oncology

Pori, Finland, 28500

Tampere University Hospital; Dept of Oncology

Tampere, Finland, 33520

Turku Uni Central Hospital; Oncology Clinics

Turku, Finland, 20520

France

Clinique De L Europe; Radiotherapie Chimiotherapie

Amiens, France, 80090

ICO Paul Papin; Oncologie Medicale.

Angers, France, 49055

Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie

Bordeaux, France, 33077

Centre Hospitalier Fleyriat; Oncologie/Hematologie

Bourg En Bresse, France, 01012

Centre Leonard De Vinci;Chimiotherapie

Dechy, France, 59187

Fondation Clement Drevon; Oncology

Dijon, France, 21000

Centre Georges Francois Leclerc; Oncologie 3

Dijon, France, 21079

Clinique Sainte Marguerite; Oncologie Medicale

Hyeres, France, 83400

Polyclinique de Blois; Chimiotherapie Ambulatoire

La Chaussee St Victor, France, 41260

Clinique Victor Hugo

LeMans, France, 72000

Polyclinique Du Bois; Centre Bourgogne

Lille, France, 59000

Clinique Chenieux; Oncology

Limoges, France, 87039

Centre Leon Berard; Departement Oncologie Medicale

Lyon, France, 69373

Institut Paoli Calmettes; Oncologie Medicale

Marseille, France, 13273

Centre Azureen De Cancerologie; Cons externes

Mougins, France, 06250

Hopital Cochin; Unite Fonctionnelle D Oncologie

Paris, France, 75014

Hopital Hotel Dieu; Oncologie Medicale

Paris, France, 75181

Institut Curie; Oncologie Medicale

Paris, France, 75231

Hopital Saint Louis; Service Onco Thoracique

Paris, France, 75475

Centre Catalan D' Oncologie

Perpignan, France, 66000

Polyclinique De Courlancy; Centre Radiotherapie Oncologie

Reims, France, 51057

Centre Eugene Marquis; Unite Huguenin

Rennes, France, 35042

Centre Rene Huguenin; ONCOLOGIE GENETIQUE

Saint Cloud, France, 92210

Chp Saint Gregoire; Cancerologie Radiotherapie

Saint Gregoire, France, 35768

Ico Rene Gauducheau; Oncologie

Saint Herblain, France, 44805

Institut D Oncologie Medical

Strasbourg, France, 67000

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, France, 31059

Hopital Prive Drome Ardeche; Hopital De Jour

Valence, France, 26000

Clinique Onco Des Dentellieres; Chimiotherapie Radiotherapie

Valenciennes, France, 59300

Germany

Klinikum am Bruderwald; Frauenklinik

Bamberg, Germany, 96049

Gynaekologicum Bremen; Prof. Dr. Willibald Schröder

Bremen, Germany, 28211

Universitätsklinikum Erlangen; Frauenklinik

Erlangen, Germany, 91054

Universitätsklinikum Essen; Zentrum Für Frauenheilkunde

Essen, Germany, 45122

Klinikum Esslingen; Klinik für Frauenheilkunde und Geburtshilfe

Esslingen, Germany, 73730

AGAPLESION Markus-Krankenhaus

Frankfurt, Germany, 60431

SRH Wald-Klinikum Gera; Klinik für Frauenheilkunde und Geburtshilfe

Gera, Germany, 07548

Universitätsklinikum Hamburg-Eppendorf; Frauenklinik

Hamburg, Germany, 20246

Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding

Hannover, Germany, 30177

Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg

Heidelberg, Germany, 69120

Universitätsklinikum des Saarlandes; Klinik f. Frauenheilkunden und Geburtshilfe

Homburg/Saar, Germany, 66424

St.-Vincenz-Krankenhaus; Frauenklinik

Limburg, Germany, 65549

Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Frauenheilkunde und Geburtshilfe

Lübeck, Germany, 23538

Brustzentrum Rhein-Ruhr Servicegesellschaft mbH

Mönchengladbach, Germany, 41061

Klinikum rechts der Isar der TU München; Klinik und Poliklinik für Frauenheilkunde

München, Germany, 81675

Ruppiner Kliniken, Klinik fuer Gynaekologie und Geburtshilfe

Neuruppin, Germany, 16816

Agaplesion Diakonieklinikum Rotenburg

Rotenburg/Wümme, Germany, 27356

Praxis Dr. Wagner

Saarbruecken, Germany, 66113

Kreiskrankenhaus Torgau; Abt.Gynäkologie und Geburtshilfe

Torgau, Germany, 04860

Universitätsklinik Tübingen; Frauenklinik

Tübingen, Germany, 72076

Greece

Anticancer Hospital Ag. Savas ; 2Nd Dept. of Oncology - Internal Medicine

Athens, Greece, 115 22

University General Hospital of Heraklion

Crete, Greece, 711 10

University Hospital of Patras Medical Oncology

Patras, Greece, 265 04

Euromedical General Clinic of Thessaloniki; Oncology Department

Thessaloniki, Greece, 546 45

Papageorgiou General Hospital; Medical Oncology

Thessaloniki, Greece, 564 29

Hippokratio Hospital; 2Nd Internal Medicine

Αθηνα, Greece, 115 27

University Hospital of Larissa; Oncology

Λαρισα, Greece, 413 35

Hong Kong

Queen Elizabeth Hospital; Clinical Oncology

Hong Kong, Hong Kong

Hungary

Szent Margit Hospital; Dept. of Oncology

Budapest, Hungary, 1032

Fovarosi Szent Laszlo Korhaz-Rendelointezet; Onkologiai Osztaly X

Budapest, Hungary, 1097

Orszagos Onkologial Intezet; Onkologiai Osztaly X

Budapest, Hungary, 1122

Debreceni Egyetem Klinikai Kozpont ; Department of Oncology

Debrecen, Hungary, 4032

Borsod-Abauj-Zemplen Megyei Korhaz Es Egyetemi Oktato Korhaz; Onkologiai Osztaly

Miskolc, Hungary, 3501

Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika

Szeged, Hungary, 6720

Israel

Soroka Medical Center; Oncology Dept

Beer Sheva, Israel, 8410100

Rambam Medical Center; Oncology

Haifa, Israel, 3109601

Wolfson Hospital; Oncology

Holon, Israel, 5822012

Shaare Zedek Medical Center; Oncology Dept

Jerusalem, Israel, 9103102

Hadassah Ein Karem Hospital; Oncology Dept

Jerusalem, Israel, 9112000

Nahariya Hospital; Oncology

Nahariya, Israel, 22100

Rabin Medical Center; Oncology Dept

Petach Tikva, Israel, 4941492

Chaim Sheba Medical Center; Oncology Dept

Ramat Gan, Israel, 5262100

Kaplan Medical Center; Oncology Inst.

Rehovot, Israel, 7610001

Sourasky / Ichilov Hospital; Dept. of Oncology

Tel Aviv, Israel, 6423906

Assuta Medical Centre; Oncology

Tel Aviv, Israel

Assaf Harofeh; Oncology

Zerifin, Israel, 6093000

Italy

Azienda Ospedaliera San Giuseppe Moscati

Avellino, Campania, Italy, 83100

Az. Osp. Ospedale Civile; U.O. Di Oncologia Medica Ed Ematologia

Piacenza, Emilia-Romagna, Italy, 29100

Azienda USL di Ravenna; Unità Operativa di Oncologia Medica

Ravenna, Emilia-Romagna, Italy, 48100

Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia

Udine, Friuli-Venezia Giulia, Italy, 33100

Ospedale Belcolle Di Viterbo; Oncologia

Viterbo, Lazio, Italy, 01100

Ente Ospedaliero Ospedali Galliera; S.C. Oncologia Medica

Genova, Liguria, Italy, 16128

Asst Papa Giovanni XXIII; Oncologia Medica

Bergamo, Lombardia, Italy, 24127

Ospedale Mater Salutis; Dept of Oncology

Legnago, Lombardia, Italy, 37045

Irccs Ospedale San Raffaele;Oncologia Medica

Milano, Lombardia, Italy, 20132

Istituto Europeo Di Oncologia

Milano, Lombardia, Italy, 20141

Irccs Policlinico S. Matteo - Uni Pavia; Clinica Medica I Div. Med. Int. Onc. Medica E Gastroent.

Pavia, Lombardia, Italy, 27100

Ospedali Riuniti Di Ancona; Oncology

Ancona, Marche, Italy, 60121

Ospedale Di Macerata; Oncologia

Macerata, Marche, Italy, 62100

Ospedale Maggiore Della Carita; Oncologia Medica

Novara, Piemonte, Italy, 28100

Ospedale Degli Infermi Di Biella; Reparto Oncologia Medica

Ponderano (BI), Piemonte, Italy, 13875

Fondazione Del Piemonte; Medical Oncology

Torino, Piemonte, Italy, 70060

Ospedale S. Vincenzo; Oncologia Medica

Taormina, Sicilia, Italy, 98030

Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1

Firenze, Toscana, Italy, 50139

Arcispedale S.Anna; Oncologia Medica

Cona (Ferrara), Veneto, Italy, 44124

Lebanon

American University of Beirut - Medical Center

Beirut, Lebanon, 1107 2020

Hotel Dieu de France; Oncology

Beirut, Lebanon, 2063 1111

Lithuania

Hospital of Lithuanian University of Health. Sciences Kaunas Clinics

Kaunas, Lithuania, 50009

Uni Oncology Inst. ; Chemo - Radiation Dept

Vilnius, Lithuania, 08660

Mexico

Iem-Fucam

D.f., Mexico, 04980

Medica Sur Centro Oncologico Integral

D.f., Mexico, 14050

Instituto Nacional de Cancerologia; Oncology

Distrito Federal, Mexico, 14080

Consultorio de Medicina Especializada; Dentro de Condominio San Francisco

Mexico City, Mexico, 03100

Centro Medico Nacional Siglo Xxi - Imss; Hospital de Oncologia

Mexico City, Mexico, 06720

Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán

Mexico City, Mexico, Tlalpan 14000

Hospital General de México; Unidad de Oncologia

Mexico DF, Mexico, 06726

Cancerologia de Queretaro; Oncologia

Queretaro, Queretaro, Mexico, 76090

Morocco

Institut National D'oncologie Sidi Mohammed Ben Abdellah; Anatomopathologie

Rabat, Morocco, 10000

Netherlands

Medisch Centrum Alkmaar

Alkmaar, Netherlands, 1815 JD

Albert Schweitzer Ziekenhuis

Dordrecht, Netherlands, 3318 AT

Catharina ZKHS; Inwendige Geneeskunde Afd.

Eindhoven, Netherlands, 5623 EJ

Martini Ziekenhuis; Dept of Internal Medicine

Groningen, Netherlands, 9728 NT

Mc Haaglanden, Locatie Antoniushove; Interne Geneeskunde

Leidschendam, Netherlands, 2262 BA

Ikazia Ziekenhuis; Interne Oncologie

Rotterdam, Netherlands, 3083 AN

Twee Steden Ziekenhuis - Locatie Tilburg; Interne Geneesekunde

Tilburg, Netherlands, 5042 AD

Vie Curie

Venlo, Netherlands, 5912 BL

Pakistan

Shifa International Hospital; Department of Oncology

Islamabad, Pakistan, 44000

Shaukat Khanum Memorial Cancer Hospital; Department of Oncology

Lahore, Pakistan, 54000

Hameed Latif Hospital; Department of Oncology

Lahore, Pakistan, 54600

Peru

Instituto;Oncologico Miraflores

Lima, Peru, 18

Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional

Lima, Peru, Lima 41

Hospital Nacional LNS dela Policia Nacional del Perú. Unidad Onco; Deapartamento de Oncología

Lima, Peru, Lima11

Poland

Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej

Bialystok, Poland, 15-027

Świętokrzyskie Centrum Onkologii; Dział Chemioterapii

Kielce, Poland, 25-734

Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii

Kraków, Poland, 30-688

Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii; Poradnia Chemioterapii

Lodz, Poland, 93-513

Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii

Otwock, Poland, 05-400

Cent.Onkologii-Instytut im. M. S-Curie, Klinika Now. Piersi i Chirurgii Rekon

Warszawa, Poland, 02-781

Portugal

IPO de Coimbra; Servico de Oncologia Medica

Coimbra, Portugal, 3000-075

Hospital do Espirito Santo; Servico de Oncologia Medica

Evora, Portugal, 7000-811

Centro Clinico Champalimaud; Oncologia Medica

Lisboa, Portugal, 1400-038

Hospital da Luz; Departamento de Oncologia Medica

Lisboa, Portugal, 1500-650

Hospital de Santa Maria; Servico de Oncologia Medica

Lisboa, Portugal, 1649-035

Hospital Beatriz Angelo; Departamento de Oncologia

Loures, Portugal, 2674-514

IPO do Porto; Servico de Oncologia Medica

Porto, Portugal, 4200-072

Hospital de Sao Joao; Servico de Oncologia

Porto, Portugal, 4200-319

Saudi Arabia

King Faisal Specialist Hospital & Research Centre; Oncology

Riyadh, Saudi Arabia, 11211

King Abdul Aziz Medical City, King Fahd National Guard; Oncology

Riyadh, Saudi Arabia, 22490

Serbia

Institute for Onc/Rad Serbia

Belgrade, Serbia, 11000

Oncology Institute of Vojvodina

Sremska Kamenica, Serbia, 21204

Slovenia

Institute of Oncology Ljubljana

Ljubljana, Slovenia, 1000

Spain

Hospital Virgen de los Lirios; Servicio de Oncologia

Alcoy, Alicante, Spain, 03804

Hospital General de Elda; Servicio de Oncologia

Elda, Alicante, Spain, 03600

Hospital de Cabueñes; Servicio de Oncologia

Gijon, Asturias, Spain, 33394

Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

Sabadell, Barcelona, Spain, 08208

Hospital de Jerez de la Frontera; Servicio de Oncologia

Jerez de La Frontera, Cadiz, Spain, 11407

Hospital Provincial de Castellon; Servicio de Oncologia

Castellon de La Plana, Castellon, Spain, 12002

Hospital de Barbastro; Servicio de Oncologia

Barbastro, Huesca, Spain, 22300

Hospital Universitario Son Espases

Palma De Mallorca, Islas Baleares, Spain, 07014

Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia

Santiago de Compostela, LA Coruña, Spain, 15706

Complejo Hospitalario San Millan - San Pedro; Servicio de Oncologia

Logroño, LA Rioja, Spain, 26006

Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia

Las Palmas de Gran Canaria, LAS Palmas, Spain, 35016

Hospital de Gran Canaria Dr. Negrin; Servicio de Oncologia

Las Palmas de Gran Canaria, LAS Palmas, Spain, 35020

Fundacion Hospital de Alcorcon; Servicio de Oncologia

Alcorcon, Madrid, Spain, 28922

Hospital Severo Ochoa; Servicio de Oncologia

Leganes, Madrid, Spain, 28911

Clinica Universitaria de Navarra; Servicio de Oncologia

Pamplona, Navarra, Spain, 31008

Hospital Universitari Sant Joan de Reus; Servicio de Oncologia

Reus, Tarragona, Spain, 43204

Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Oncologia

Santa Cruz de Tenerife, Tenerife, Spain, 38010

Hospital de Sagunto; Servicio de Oncologia

Sagunto, Valencia, Spain, 46520

Hospital de Basurto; Servicio de Oncologia

Bilbao, Vizcaya, Spain, 48013

Hospital Quiron Barcelona; Servicio de Oncologia

Barcelona, Spain, 08024

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, Spain, 08036

Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia

Barcelona, Spain, 08041

Complejo Asistencial Universitario De Burgos; Servicio de Oncologia

Burgos, Spain, 09006

Hospital San Pedro De Alcantara; Servicio de Oncologia

Caceres, Spain, 10003

Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia

Girona, Spain, 17007

Hospital Universitario Virgen de las Nieves; Servicio de Oncologia

Granada, Spain, 18014

Hospital General Universitario de Guadalajara; Servicio de Oncologia

Guadalajara, Spain, 19002

Complejo Asistencial Universitario de Leon; Servicio de Oncologia

Leon, Spain, 24071

Centro Oncologico MD Anderson Internacional; Servicio de Oncologia

Madrid, Spain, 28033

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, Spain, 28034

Fundacion Jimenez Diaz; Servicio de Oncologia

Madrid, Spain, 28040

Hospital Universitario Clínico San Carlos; Servicio de Oncologia

Madrid, Spain, 28040

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, Spain, 28041

Hospital Universitario La Paz; Servicio de Oncologia

Madrid, Spain, 28046

HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia

Madrid, Spain, 28050

Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia

Malaga, Spain, 29010

Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia

Murcia, Spain, 30008

Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia

Murcia, Spain, 30120

Hospital de Navarra; Servicio de Oncologia

Navarra, Spain, 31008

Complejo Hospitalario de Orense; Servicio de Oncologia

Orense, Spain, 32005

Hospital Clinico Universitario de Salamanca; Servicio de Oncologia

Salamanca, Spain, 37007

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Sevilla, Spain, 41009

Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia

Valencia, Spain, 46015

Hospital Universitario Dr. Peset

Valencia, Spain, 46017

Hospital Clinico Universitario de Valladolid; Servicio de Oncologia

Valladolid, Spain, 47005

Hospital de Rio Hortega; Servicio de Oncologia

Valladolid, Spain, 47010

Hospital Clinico Universitario Lozano Blesa; Servicio de Oncologia

Zaragoza, Spain, 50009

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, Spain, 50009

Sweden

Gävle Sjukhus; Onkologiska Kliniken

Gävle, Sweden, 80187

Sahlgrenska Universitetssjukhuset; Jubileumskliniken

Göteborg, Sweden, 413 45

Centralsjukhuset Karlstad, Onkologkliniken

Karlstad, Sweden, 65185

Skånes University Hospital, Skånes Department of Onclology

Lund, Sweden, 221 85

Centrallasarettet Växjö, Onkologkliniken

Vaxjo, Sweden, 35185

Västmanlands sjukhus Västerås, Onkologkliniken

Västerås, Sweden, 72189

Turkey

Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology

Adana, Turkey, 01250

Akdeniz University Medical Faculty; Medical Oncology Department

Antalya, Turkey, 07070

Ege University Medical Faculty; Medical Oncology Department

Bornova, İ̇zmi̇r, Turkey, 35100

Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department

Edirne, Turkey, 22770

Hacettepe Uni Medical Faculty Hospital; Oncology Dept

Sihhiye/Ankara, Turkey, 06230

Ukraine

Mun. Multifield Clin.Hosp.#4,Dept. of Chemotherapy, DSMU; Chair of Oncology and Medical Radiology

Dnipropetrovsk, Ukraine, 49102

Kyiv City Clinical Oncological Center; Chemotherapy Department

Kiev, Ukraine, 03115

State Oncology Regional Treatment-Diagnostic Center; Chemotherapy Department

Lviv, Ukraine, 79031

Zaporozhye Regional Oncology Hospital; Dept of Oncology

Zaporozhye, Ukraine, 69104

United Arab Emirates

Tawam Hospital

Al Ain, United Arab Emirates, 15258

United Kingdom

Royal United Hospital; Oncology Department

Bath, United Kingdom, BA1 3NG

City Hospital NHS Trust

Birmingham, United Kingdom, B18 7QH

Bristol Haematology and Oncology Centre

Bristol, United Kingdom, BS2 8ED

Addenbrookes Hospital; Dept of Oncology

Cambridge, United Kingdom, CB2 2QQ

Velindre Hospital

Cardiff, United Kingdom, CF14 2TL

Walsgrave Hospital

Coventry, United Kingdom, CV2 2DX

Royal Derby Hospital

Derby, United Kingdom, DE22 3NE

University Hospital of North Durham

Durham, United Kingdom, DH15TW

Hairmyres Hospital; Oncology Dept

East Kilbride, United Kingdom, G75 8RG

Eastbourne District Hospital; Department of Pharmacy

Eastbourne, United Kingdom, BN21 2UD

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom, G12 0YN

Diana Princess of Wales Hosp.

Grimsby, United Kingdom, DN33 2BA

Royal Surrey County Hospital

Guildford, United Kingdom, GU2 7XX

Leeds Teaching Hosp NHS Trust;St James's Institute of Onc

Leeds, United Kingdom, LS9 7TF

Huddersfield Royal Infirmary - Pharmacy department

Lindley, United Kingdom, HD3 3EA

Barts and the London NHS Trust.

London, United Kingdom, EC1A 7BE

Royal Free Hospital; Dept of Oncology

London, United Kingdom, NW3 2QG

Kings College Hospital NHS Foundation Trust

London, United Kingdom, SE5 9RS

Royal Marsden Hospital - London

London, United Kingdom, SW3 6JJ

Macclesfield District General Hospital

Macclesfield, United Kingdom, SK10 3BL

Christie Hospital; Breast Cancer Research Office

Manchester, United Kingdom, M20 4QL

James Cook Uni Hospital

Middlesborough, United Kingdom, TS4 3BW

Freeman Hospital; Northern Centre For Cancer Care

New Castle Upon Tyne, United Kingdom, NE7 7DN

Mount Vernon Cancer Centre

Northwood, United Kingdom, HA6 2RN

Churchill Hospital

Oxford, United Kingdom, OX3 7LJ

Peterborough City Hospital

Peterborough, United Kingdom, PE3 9GZ

Derriford Hospital; Plymouth Oncology Centre

Plymouth, United Kingdom, PL6 8DH

Musgrove Park Hospital

Somerset, United Kingdom, TA1 5DA

The Royal Marsden Hospital

Sutton, United Kingdom, SM2 5PT

Royal Cornwall Hospital

Truro, United Kingdom, TR1 3LQ

Wishaw General Hospital

Wishaw, United Kingdom, ML2 0DP

Uruguay

Grupo Oncológico Cooperativo Uruguayo; Hospital de Clínicas - Dpto. de Oncología

Montevideo, Uruguay, 11400

Hospital Central De Las FF.AA.; Servicio De Oncologia

Montevideo, Uruguay, 11600

Hospital Pereira Rossell; Oncology Department

Montevideo, Uruguay, 11600

Venezuela

Centro Integral de Oncología

Caracas, Venezuela, 1060

Centro Médico Docente La Trinidad; Servicio de Gastroenterología

Caracas, Venezuela, 1080

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:

Study Protocol  [PDF] November 21, 2018

Statistical Analysis Plan  [PDF] November 25, 2019

More Information

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

Bachelot T, Ciruelos E, Schneeweiss A, Puglisi F, Peretz-Yablonski T, Bondarenko I, Paluch-Shimon S, Wardley A, Merot JL, du Toit Y, Easton V, Lindegger N, Miles D; PERUSE investigators. Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE). Ann Oncol. 2019 May 1;30(5):766-773. doi: 10.1093/annonc/mdz061.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01572038
• Other Study ID Numbers: MO28047; 2011-005334-20 ( EudraCT Number )
• First Posted: April 5, 2012
• Results First Posted: September 25, 2020
• Last Update Posted: September 25, 2020
• Last Verified: August 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Docetaxel; Albumin-Bound Paclitaxel; Trastuzumab; Pertuzumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological