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

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

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

Layout table for study information
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01572038


Locations
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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
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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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01572038    
Other Study ID Numbers: MO28047
2011-005334-20 ( EudraCT Number )
First Posted: April 5, 2012    Key Record Dates
Results First Posted: September 25, 2020
Last Update Posted: September 25, 2020
Last Verified: August 2020

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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:
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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