Clinical Trials/NCT01572038

NCT01572038

Completed

Phase 3

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

Hoffmann-La Roche299 sites in 9 countries1,436 target enrollmentJune 1, 2012

ConditionsBreast Neoplasms

InterventionsDocetaxel Nab-paclitaxel Paclitaxel Pertuzumab Trastuzumab

DrugsDocetaxel Nab-paclitaxel Paclitaxel Pertuzumab Trastuzumab

Overview

Phase: Phase 3
Intervention: Docetaxel
Conditions: Breast Neoplasms
Sponsor: Hoffmann-La Roche
Enrollment: 1436
Locations: 299
Primary Endpoint: 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
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

June 1, 2012

End Date

September 20, 2019

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility 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

Arms & Interventions

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.

Intervention: Docetaxel

Pertuzumab + Trastuzumab + Taxane

Intervention: Nab-paclitaxel

Pertuzumab + Trastuzumab + Taxane

Intervention: Paclitaxel

Pertuzumab + Trastuzumab + Taxane

Intervention: Pertuzumab

Pertuzumab + Trastuzumab + Taxane

Intervention: Trastuzumab

Outcomes

Primary Outcomes

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.

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

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

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).

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)

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.

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

Number of Participants With Treatment-Emergent Adverse Events to Monitor of Any Grade, Occurring in ≥5% of Participants by Category

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.

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

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.

Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events, Occurring in ≥1% of Participants by System Organ Class and Preferred Term

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.

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

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.

Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events to Monitor, Occurring in ≥0.5% of Participants by Category and Preferred Term

Number of Participants With Treatment-Emergent Adverse Events of Special Interest by Category and Preferred Term

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.

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

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.

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

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

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.

Number of Participants With Laboratory Abnormalities in Biochemistry Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to Normal Range Criteria

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.

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

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.

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

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

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 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.

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

Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Values Over the Course of the Study

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.

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

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.

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

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.

Secondary Outcomes

Subgroup Analysis by ECOG Performance Status at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1(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.)
Subgroup Analysis by Age (≤65 vs. >65 Years): Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1(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.)
Subgroup Analysis by ECOG Performance Status at Baseline: Overall Survival(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.)
Subgroup Analysis by Taxane Chemotherapy: Overall Survival(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.)
Progression-Free Survival, as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)(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.)
Subgroup Analysis by Prior (Neo)Adjuvant Chemotherapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1(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.)
Overall Survival(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.)
Subgroup Analysis by Region of Enrollment: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1(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.)
Subgroup Analysis by Previous Trastuzumab Therapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1(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.)
Subgroup Analysis by Age (≤65 vs. >65 Years): Overall Survival(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.)
Subgroup Analysis by Taxane Chemotherapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1(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.)
Subgroup Analysis by Hormone Receptor Status at Baseline: Overall Survival(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.)
Subgroup Analysis by Previous Trastuzumab Therapy: Overall Survival(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.)
Subgroup Analysis by Visceral Disease at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1(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.)
Subgroup Analysis by Hormone Receptor Status at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1(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.)
Subgroup Analysis by Region of Enrollment: Overall Survival(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.)
Change From Baseline in FACT-B Questionnaire Functional Well-Being Subscale Score Over the Course of the Study(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.)
Overall Response Rate (Complete Response or Partial Response) Based on Best Overall Response (Confirmed) as Assessed by the Investigator Using RECIST v1.1(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.)
Percentage of Participants by Best Overall Response as Assessed by the Investigator Using RECIST v1.1(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.)
Subgroup Analysis by Visceral Disease at Baseline: Overall Survival(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.)
Subgroup Analysis by Prior (Neo)Adjuvant Chemotherapy: Overall Survival(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.)
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(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.)
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(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.)
Duration of Response as Assessed by the Investigator Using RECIST v1.1(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.)
Change From Baseline in FACT-B Questionnaire Social Well-Being Subscale Score Over the Course of the Study(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.)
Change From Baseline in FACT-B Questionnaire Emotional Well-Being Subscale Score Over the Course of the Study(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.)
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(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.)
Time to Response for Participants With Best Overall Response of Complete Response or Partial Response, as Assessed by the Investigator Using RECIST v1.1(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.)
Change From Baseline in Functional Assessment of Cancer Therapy - Breast Cancer (FACT-B) Questionnaire Total Score Over the Course of the Study(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.)
Change From Baseline in FACT-B Questionnaire Physical Well-Being Subscale Score Over the Course of the Study(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.)
Change From Baseline in FACT-B Questionnaire Breast Cancer Subscale Score Over the Course of the Study(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.)