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
- Conditions
- Breast Neoplasms
- Interventions
- Registration Number
- NCT01572038
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1436
- 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 (%)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Pertuzumab + Trastuzumab + Taxane Nab-paclitaxel 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. Pertuzumab + Trastuzumab + Taxane Docetaxel 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. Pertuzumab + Trastuzumab + Taxane Paclitaxel 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. Pertuzumab + Trastuzumab + Taxane Pertuzumab 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. Pertuzumab + Trastuzumab + Taxane Trastuzumab 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.
- Primary Outcome Measures
Name Time Method 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 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) 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 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.
Number of Participants With a Congestive Heart Failure Event 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) 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.
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 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
Number of Participants With Treatment-Emergent Adverse Events to Monitor of Any Grade, Occurring in ≥5% of Participants by Category 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.
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 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.
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) 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
Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events, Occurring in ≥1% of Participants by System Organ Class and Preferred Term 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.
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 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.
Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events to Monitor, Occurring in ≥0.5% of Participants by Category and Preferred Term 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.
Number of Participants With Treatment-Emergent Adverse Events of Special Interest by Category and Preferred Term 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.
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 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.
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 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
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 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.
Number of Participants With Laboratory Abnormalities in Biochemistry Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to NCI-CTC v4.0 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 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.
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 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.
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 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.
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 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.
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 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.
Time to Onset of the First Episode of Congestive Heart Failure 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 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 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.
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 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.
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 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.
- Secondary Outcome Measures
Name Time Method 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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
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. 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.
Trial Locations
- Locations (299)
Centro Oncologico Riojano Integral (CORI)
🇦🇷La Rioja, Argentina
LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie
🇦🇹Graz, Austria
UZ Brussel
🇧🇪Brussel, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Oncologistas Associados
🇧🇷Rio de Janeiro, RJ, Brazil
Mater Hospital; Cancer Services
🇦🇺South Brisbane, Queensland, Australia
Lkh-Univ. Klinikum Graz; Klinik Für Gynäkologie
🇦🇹Graz, Austria
Southwest Hospital , Third Military Medical University
🇨🇳Chongqing, China
HOCA Chermside
🇦🇺Chermside, Queensland, Australia
Sun Yet-sen University Cancer Center
🇨🇳Guangzhou, China
Royal Prince Alfred Hospital; Medical Oncology
🇦🇺Camperdown, New South Wales, Australia
CHU Sart-Tilman
🇧🇪Liège, Belgium
Beijing Cancer Hospital
🇨🇳Beijing, China
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, RS, Brazil
Hospital Amaral Carvalho
🇧🇷Jau, SP, Brazil
Clinique Victor Hugo
🇫🇷LeMans, France
Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie
🇫🇷Bordeaux, France
Clinique Sainte Marguerite; Oncologie Medicale
🇫🇷Hyeres, France
Polyclinique de Blois; Chimiotherapie Ambulatoire
🇫🇷La Chaussee St Victor, France
Hopital Saint Louis; Service Onco Thoracique
🇫🇷Paris, France
Universitätsklinikum des Saarlandes; Klinik f. Frauenheilkunden und Geburtshilfe
🇩🇪Homburg/Saar, Germany
University Hospital of Larissa; Oncology
🇬🇷Λαρισα, Greece
Instituto Nacional de Cancerologia; Oncology
🇲🇽Distrito Federal, Mexico
Hospital Quiron Barcelona; Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital Provincial de Castellon; Servicio de Oncologia
🇪🇸Castellon de La Plana, Castellon, Spain
Hospital de Jerez de la Frontera; Servicio de Oncologia
🇪🇸Jerez de La Frontera, Cadiz, Spain
Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán
🇲🇽Mexico City, Mexico
Shaukat Khanum Memorial Cancer Hospital; Department of Oncology
🇵🇰Lahore, Pakistan
Catharina ZKHS; Inwendige Geneeskunde Afd.
🇳🇱Eindhoven, Netherlands
Mc Haaglanden, Locatie Antoniushove; Interne Geneeskunde
🇳🇱Leidschendam, Netherlands
Ikazia Ziekenhuis; Interne Oncologie
🇳🇱Rotterdam, Netherlands
Hospital de Basurto; Servicio de Oncologia
🇪🇸Bilbao, Vizcaya, Spain
Hospital San Pedro De Alcantara; Servicio de Oncologia
🇪🇸Caceres, Spain
Martini Ziekenhuis; Dept of Internal Medicine
🇳🇱Groningen, Netherlands
Centro Clinico Champalimaud; Oncologia Medica
🇵🇹Lisboa, Portugal
Complejo Asistencial Universitario De Burgos; Servicio de Oncologia
🇪🇸Burgos, Spain
Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia
🇪🇸Girona, Spain
Complejo Hospitalario San Millan - San Pedro; Servicio de Oncologia
🇪🇸Logroño, LA Rioja, Spain
Shifa International Hospital; Department of Oncology
🇵🇰Islamabad, Pakistan
Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej
🇵🇱Bialystok, Poland
Centro Oncologico MD Anderson Internacional; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario Virgen de las Nieves; Servicio de Oncologia
🇪🇸Granada, Spain
Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
🇪🇸Malaga, Spain
Fundacion Jimenez Diaz; Servicio de Oncologia
🇪🇸Madrid, Spain
Peterborough City Hospital
🇬🇧Peterborough, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
Hospital Central De Las FF.AA.; Servicio De Oncologia
🇺🇾Montevideo, Uruguay
Mount Vernon Cancer Centre
🇬🇧Northwood, United Kingdom
Derriford Hospital; Plymouth Oncology Centre
🇬🇧Plymouth, United Kingdom
Wishaw General Hospital
🇬🇧Wishaw, United Kingdom
Musgrove Park Hospital
🇬🇧Somerset, United Kingdom
The Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Heilongjiang Provincial Tumor Hospital
🇨🇳Harbin, China
The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)
🇨🇳Xi'an, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
🇨🇳Xi'an, China
Satakunta Central Hospital; Oncology
🇫🇮Pori, Finland
Tampere University Hospital; Dept of Oncology
🇫🇮Tampere, Finland
Centre Eugene Marquis; Unite Huguenin
🇫🇷Rennes, France
Institut D Oncologie Medical
🇫🇷Strasbourg, France
Hopital Prive Drome Ardeche; Hopital De Jour
🇫🇷Valence, France
Clinique Onco Des Dentellieres; Chimiotherapie Radiotherapie
🇫🇷Valenciennes, France
Klinikum Esslingen; Klinik für Frauenheilkunde und Geburtshilfe
🇩🇪Esslingen, Germany
AGAPLESION Markus-Krankenhaus
🇩🇪Frankfurt, Germany
SRH Wald-Klinikum Gera; Klinik für Frauenheilkunde und Geburtshilfe
🇩🇪Gera, Germany
Agaplesion Diakonieklinikum Rotenburg
🇩🇪Rotenburg/Wümme, Germany
Kreiskrankenhaus Torgau; Abt.Gynäkologie und Geburtshilfe
🇩🇪Torgau, Germany
University Hospital of Patras Medical Oncology
🇬🇷Patras, Greece
Euromedical General Clinic of Thessaloniki; Oncology Department
🇬🇷Thessaloniki, Greece
Szent Margit Hospital; Dept. of Oncology
🇭🇺Budapest, Hungary
Orszagos Onkologial Intezet; Onkologiai Osztaly X
🇭🇺Budapest, Hungary
Hadassah Ein Karem Hospital; Oncology Dept
🇮🇱Jerusalem, Israel
Hospital of Lithuanian University of Health. Sciences Kaunas Clinics
🇱🇹Kaunas, Lithuania
Ospedali Riuniti Di Ancona; Oncology
🇮🇹Ancona, Marche, Italy
Chaim Sheba Medical Center; Oncology Dept
🇮🇱Ramat Gan, Israel
Kaplan Medical Center; Oncology Inst.
🇮🇱Rehovot, Israel
Istituto Europeo Di Oncologia
🇮🇹Milano, Lombardia, Italy
Ospedale Di Macerata; Oncologia
🇮🇹Macerata, Marche, Italy
Ospedale Belcolle Di Viterbo; Oncologia
🇮🇹Viterbo, Lazio, Italy
Ospedale Maggiore Della Carita; Oncologia Medica
🇮🇹Novara, Piemonte, Italy
Hospital General de México; Unidad de Oncologia
🇲🇽Mexico DF, Mexico
Hospital de Sagunto; Servicio de Oncologia
🇪🇸Sagunto, Valencia, Spain
Hospital Severo Ochoa; Servicio de Oncologia
🇪🇸Leganes, Madrid, Spain
Fundacion Hospital de Alcorcon; Servicio de Oncologia
🇪🇸Alcorcon, Madrid, Spain
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom
Hospital Ramon y Cajal; Servicio de Oncologia
🇪🇸Madrid, Spain
Centre Georges Francois Leclerc; Oncologie 3
🇫🇷Dijon, France
CPMC; Service d'Oncologie Médicale
🇩🇿Algiers, Algeria
Instituto de Oncología de Rosario
🇦🇷Rosario, Argentina
Canberra Hospital; Medical Oncology
🇦🇺Canberra, Australian Capital Territory, Australia
Royal Melbourne Hospital; Hematology and Medical Oncology
🇦🇺Parkville, Victoria, Australia
Queen Elizabeth II Health Sciences Centre; Oncology
🇨🇦Halifax, Nova Scotia, Canada
Centre Leonard De Vinci;Chimiotherapie
🇫🇷Dechy, France
Sunnybrook Odette Cancer Centre
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier Fleyriat; Oncologie/Hematologie
🇫🇷Bourg En Bresse, France
Tianjin Cancer Hospital
🇨🇳Tianjin, China
Nci; Oncology Dept
🇪🇬Cairo, Egypt
North Estonia Medical Centre Foundation; Oncology Center
🇪🇪Tallinn, Estonia
Helsinki University Central Hospital; Oncology Clinics
🇫🇮Helsinki, Finland
Hopital Hotel Dieu; Oncologie Medicale
🇫🇷Paris, France
Chp Saint Gregoire; Cancerologie Radiotherapie
🇫🇷Saint Gregoire, France
Universitätsklinikum Essen; Zentrum Für Frauenheilkunde
🇩🇪Essen, Germany
Klinikum rechts der Isar der TU München; Klinik und Poliklinik für Frauenheilkunde
🇩🇪München, Germany
Shaare Zedek Medical Center; Oncology Dept
🇮🇱Jerusalem, Israel
Nahariya Hospital; Oncology
🇮🇱Nahariya, Israel
Sourasky / Ichilov Hospital; Dept. of Oncology
🇮🇱Tel Aviv, Israel
Assuta Medical Centre; Oncology
🇮🇱Tel Aviv, Israel
Azienda Ospedaliera San Giuseppe Moscati
🇮🇹Avellino, Campania, Italy
Ente Ospedaliero Ospedali Galliera; S.C. Oncologia Medica
🇮🇹Genova, Liguria, Italy
Medica Sur Centro Oncologico Integral
🇲🇽D.f., Mexico
Iem-Fucam
🇲🇽D.f., Mexico
Fondazione Del Piemonte; Medical Oncology
🇮🇹Torino, Piemonte, Italy
Ospedale S. Vincenzo; Oncologia Medica
🇮🇹Taormina, Sicilia, Italy
Cancerologia de Queretaro; Oncologia
🇲🇽Queretaro, Queretaro, Mexico
Institut National D'oncologie Sidi Mohammed Ben Abdellah; Anatomopathologie
🇲🇦Rabat, Morocco
Vie Curie
🇳🇱Venlo, Netherlands
Twee Steden Ziekenhuis - Locatie Tilburg; Interne Geneesekunde
🇳🇱Tilburg, Netherlands
Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii
🇵🇱Kraków, Poland
Hospital de Sao Joao; Servico de Oncologia
🇵🇹Porto, Portugal
King Abdul Aziz Medical City, King Fahd National Guard; Oncology
🇸🇦Riyadh, Saudi Arabia
Oncology Institute of Vojvodina
🇷🇸Sremska Kamenica, Serbia
Hospital General de Elda; Servicio de Oncologia
🇪🇸Elda, Alicante, Spain
Hospital de Cabueñes; Servicio de Oncologia
🇪🇸Gijon, Asturias, Spain
Hospital de Barbastro; Servicio de Oncologia
🇪🇸Barbastro, Huesca, Spain
Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
🇪🇸Santiago de Compostela, LA Coruña, Spain
Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Oncologia
🇪🇸Santa Cruz de Tenerife, Tenerife, Spain
Hospital Universitario Son Espases
🇪🇸Palma De Mallorca, Islas Baleares, Spain
Hospital Clínic i Provincial; Servicio de Hematología y Oncología
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital General Universitario de Guadalajara; Servicio de Oncologia
🇪🇸Guadalajara, Spain
Complejo Asistencial Universitario de Leon; Servicio de Oncologia
🇪🇸Leon, Spain
Hospital Universitario Clínico San Carlos; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario La Paz; Servicio de Oncologia
🇪🇸Madrid, Spain
HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia
🇪🇸Murcia, Spain
Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia
🇪🇸Murcia, Spain
Hospital de Navarra; Servicio de Oncologia
🇪🇸Navarra, Spain
Complejo Hospitalario de Orense; Servicio de Oncologia
🇪🇸Orense, Spain
Hospital Universitario Virgen Macarena; Servicio de Oncologia
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Salamanca; Servicio de Oncologia
🇪🇸Salamanca, Spain
Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia
🇪🇸Valencia, Spain
Hospital Universitario Dr. Peset
🇪🇸Valencia, Spain
Hospital Clinico Universitario de Valladolid; Servicio de Oncologia
🇪🇸Valladolid, Spain
Hospital Clinico Universitario Lozano Blesa; Servicio de Oncologia
🇪🇸Zaragoza, Spain
Hospital Universitario Miguel Servet; Servicio Oncologia
🇪🇸Zaragoza, Spain
Sahlgrenska Universitetssjukhuset; Jubileumskliniken
🇸🇪Göteborg, Sweden
Gävle Sjukhus; Onkologiska Kliniken
🇸🇪Gävle, Sweden
Centralsjukhuset Karlstad, Onkologkliniken
🇸🇪Karlstad, Sweden
Skånes University Hospital, Skånes Department of Onclology
🇸🇪Lund, Sweden
Centrallasarettet Växjö, Onkologkliniken
🇸🇪Vaxjo, Sweden
Västmanlands sjukhus Västerås, Onkologkliniken
🇸🇪Västerås, Sweden
Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology
🇹🇷Adana, Turkey
Akdeniz University Medical Faculty; Medical Oncology Department
🇹🇷Antalya, Turkey
Ege University Medical Faculty; Medical Oncology Department
🇹🇷Bornova, İ̇zmi̇r, Turkey
Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department
🇹🇷Edirne, Turkey
Kyiv City Clinical Oncological Center; Chemotherapy Department
🇺🇦Kiev, Ukraine
Mun. Multifield Clin.Hosp.#4,Dept. of Chemotherapy, DSMU; Chair of Oncology and Medical Radiology
🇺🇦Dnipropetrovsk, Ukraine
Hacettepe Uni Medical Faculty Hospital; Oncology Dept
🇹🇷Sihhiye/Ankara, Turkey
State Oncology Regional Treatment-Diagnostic Center; Chemotherapy Department
🇺🇦Lviv, Ukraine
Zaporozhye Regional Oncology Hospital; Dept of Oncology
🇺🇦Zaporozhye, Ukraine
Tawam Hospital
🇦🇪Al Ain, United Arab Emirates
Royal United Hospital; Oncology Department
🇬🇧Bath, United Kingdom
Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
City Hospital NHS Trust
🇬🇧Birmingham, United Kingdom
Addenbrookes Hospital; Dept of Oncology
🇬🇧Cambridge, United Kingdom
Velindre Hospital
🇬🇧Cardiff, United Kingdom
Walsgrave Hospital
🇬🇧Coventry, United Kingdom
Royal Derby Hospital
🇬🇧Derby, United Kingdom
Eastbourne District Hospital; Department of Pharmacy
🇬🇧Eastbourne, United Kingdom
University Hospital of North Durham
🇬🇧Durham, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Hairmyres Hospital; Oncology Dept
🇬🇧East Kilbride, United Kingdom
Diana Princess of Wales Hosp.
🇬🇧Grimsby, United Kingdom
Royal Surrey County Hospital
🇬🇧Guildford, United Kingdom
Leeds Teaching Hosp NHS Trust;St James's Institute of Onc
🇬🇧Leeds, United Kingdom
Huddersfield Royal Infirmary - Pharmacy department
🇬🇧Lindley, United Kingdom
Barts and the London NHS Trust.
🇬🇧London, United Kingdom
Royal Free Hospital; Dept of Oncology
🇬🇧London, United Kingdom
Macclesfield District General Hospital
🇬🇧Macclesfield, United Kingdom
Kings College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Royal Marsden Hospital - London
🇬🇧London, United Kingdom
Freeman Hospital; Northern Centre For Cancer Care
🇬🇧New Castle Upon Tyne, United Kingdom
James Cook Uni Hospital
🇬🇧Middlesborough, United Kingdom
Centro Integral de Oncología
🇻🇪Caracas, Venezuela
Centro Médico Docente La Trinidad; Servicio de Gastroenterología
🇻🇪Caracas, Venezuela
Manial Specialized Hospital; Oncology
🇪🇬Cairo, Egypt
Institut Curie; Oncologie Medicale
🇫🇷Paris, France
Hospital de Rio Hortega; Servicio de Oncologia
🇪🇸Valladolid, Spain
Hospital Solca Quito; Oncologia
🇪🇨Quito, Ecuador
Turku Uni Central Hospital; Oncology Clinics
🇫🇮Turku, Finland
Clinique De L Europe; Radiotherapie Chimiotherapie
🇫🇷Amiens, France
Fondation Clement Drevon; Oncology
🇫🇷Dijon, France
Polyclinique Du Bois; Centre Bourgogne
🇫🇷Lille, France
Institut Paoli Calmettes; Oncologie Medicale
🇫🇷Marseille, France
Centre Azureen De Cancerologie; Cons externes
🇫🇷Mougins, France
Gynaekologicum Bremen; Prof. Dr. Willibald Schröder
🇩🇪Bremen, Germany
UZ Antwerpen
🇧🇪Edegem, Belgium
Hospital das Clinicas - FMUSP
🇧🇷Sao Paulo, SP, Brazil
Hospital Solca Portoviejo; Oncologia
🇪🇨Portoviejo, Ecuador
Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding
🇩🇪Hannover, Germany
Brustzentrum Rhein-Ruhr Servicegesellschaft mbH
🇩🇪Mönchengladbach, Germany
Ruppiner Kliniken, Klinik fuer Gynaekologie und Geburtshilfe
🇩🇪Neuruppin, Germany
Anticancer Hospital Ag. Savas ; 2Nd Dept. of Oncology - Internal Medicine
🇬🇷Athens, Greece
Austin and Repatriation Medical Centre; Cancer Services
🇦🇺Melbourne, Victoria, Australia
Lions Gate Hospital
🇨🇦North Vancouver, British Columbia, Canada
Centre Leon Berard; Departement Oncologie Medicale
🇫🇷Lyon, France
Ordensklinikum Linz Barmherzige Schwestern; Abt. fur Innere Medizin 1
🇦🇹Linz, Austria
Centre Hospitalier de l'Université de Montréal (CHUM)
🇨🇦Montreal, Quebec, Canada
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
🇨🇦Montreal, Quebec, Canada
Bcca - Vancouver Island Cancer Centre; Oncology
🇨🇦Victoria, British Columbia, Canada
Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.
🇦🇹Salzburg, Austria
A.Ö. Lhk; Ii. Medizinische Abt. Mit Schwerpunkt Gaströnter. & Onkologie
🇦🇹Steyr, Austria
Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie
🇦🇹Wien, Austria
Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie
🇦🇹Wien, Austria
Hospital Perola Byington
🇧🇷Sao Paulo, SP, Brazil
ICO Paul Papin; Oncologie Medicale.
🇫🇷Angers, France
Centre Rene Huguenin; ONCOLOGIE GENETIQUE
🇫🇷Saint Cloud, France
Klinikum am Bruderwald; Frauenklinik
🇩🇪Bamberg, Germany
Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
🇩🇪Heidelberg, Germany
St.-Vincenz-Krankenhaus; Frauenklinik
🇩🇪Limburg, Germany
Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Frauenheilkunde und Geburtshilfe
🇩🇪Lübeck, Germany
Praxis Dr. Wagner
🇩🇪Saarbruecken, Germany
Universitätsklinik Tübingen; Frauenklinik
🇩🇪Tübingen, Germany
Papageorgiou General Hospital; Medical Oncology
🇬🇷Thessaloniki, Greece
Borsod-Abauj-Zemplen Megyei Korhaz Es Egyetemi Oktato Korhaz; Onkologiai Osztaly
🇭🇺Miskolc, Hungary
Rambam Medical Center; Oncology
🇮🇱Haifa, Israel
Ospedale Mater Salutis; Dept of Oncology
🇮🇹Legnago, Lombardia, Italy
Irccs Policlinico S. Matteo - Uni Pavia; Clinica Medica I Div. Med. Int. Onc. Medica E Gastroent.
🇮🇹Pavia, Lombardia, Italy
American University of Beirut - Medical Center
🇱🇧Beirut, Lebanon
UZ Gent
🇧🇪Gent, Belgium
CSSS champlain - Charles-Le Moyne
🇨🇦Greenfield Park, Quebec, Canada
Ico Rene Gauducheau; Oncologie
🇫🇷Saint Herblain, France
University General Hospital of Heraklion
🇬🇷Crete, Greece
Hippokratio Hospital; 2Nd Internal Medicine
🇬🇷Αθηνα, Greece
Soroka Medical Center; Oncology Dept
🇮🇱Beer Sheva, Israel
Wolfson Hospital; Oncology
🇮🇱Holon, Israel
Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1
🇮🇹Firenze, Toscana, Italy
Arcispedale S.Anna; Oncologia Medica
🇮🇹Cona (Ferrara), Veneto, Italy
Hotel Dieu de France; Oncology
🇱🇧Beirut, Lebanon
Uni Oncology Inst. ; Chemo - Radiation Dept
🇱🇹Vilnius, Lithuania
Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional
🇵🇪Lima, Peru
Hospital de Santa Maria; Servico de Oncologia Medica
🇵🇹Lisboa, Portugal
Hospital Virgen de los Lirios; Servicio de Oncologia
🇪🇸Alcoy, Alicante, Spain
Grand River Hospital
🇨🇦Kitchener, Ontario, Canada
Hopital Cochin; Unite Fonctionnelle D Oncologie
🇫🇷Paris, France
Fovarosi Szent Laszlo Korhaz-Rendelointezet; Onkologiai Osztaly X
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont ; Department of Oncology
🇭🇺Debrecen, Hungary
Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie
🇦🇹Innsbruck, Austria
Hospital Sirio Libanes; Centro de Oncologia
🇧🇷Sao Paulo, SP, Brazil
Tartu University Hospital; Clinic of Hematology and Oncology
🇪🇪Tartu, Estonia
Clinique Chenieux; Oncology
🇫🇷Limoges, France
Centre Catalan D' Oncologie
🇫🇷Perpignan, France
Polyclinique De Courlancy; Centre Radiotherapie Oncologie
🇫🇷Reims, France
Universitätsklinikum Erlangen; Frauenklinik
🇩🇪Erlangen, Germany
Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika
🇭🇺Szeged, Hungary
Rabin Medical Center; Oncology Dept
🇮🇱Petach Tikva, Israel
Assaf Harofeh; Oncology
🇮🇱Zerifin, Israel
Azienda USL di Ravenna; Unità Operativa di Oncologia Medica
🇮🇹Ravenna, Emilia-Romagna, Italy
Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia
🇮🇹Udine, Friuli-Venezia Giulia, Italy
Asst Papa Giovanni XXIII; Oncologia Medica
🇮🇹Bergamo, Lombardia, Italy
Irccs Ospedale San Raffaele;Oncologia Medica
🇮🇹Milano, Lombardia, Italy
Ospedale Degli Infermi Di Biella; Reparto Oncologia Medica
🇮🇹Ponderano (BI), Piemonte, Italy
Consultorio de Medicina Especializada; Dentro de Condominio San Francisco
🇲🇽Mexico City, Mexico
Centro Medico Nacional Siglo Xxi - Imss; Hospital de Oncologia
🇲🇽Mexico City, Mexico
Medisch Centrum Alkmaar
🇳🇱Alkmaar, Netherlands
Hospital Nacional LNS dela Policia Nacional del Perú. Unidad Onco; Deapartamento de Oncología
🇵🇪Lima, Peru
Institut Claudius Regaud; Departement Oncologie Medicale
🇫🇷Toulouse, France
Az. Osp. Ospedale Civile; U.O. Di Oncologia Medica Ed Ematologia
🇮🇹Piacenza, Emilia-Romagna, Italy
Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
🇪🇸Sabadell, Barcelona, Spain
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii; Poradnia Chemioterapii
🇵🇱Lodz, Poland
Hospital da Luz; Departamento de Oncologia Medica
🇵🇹Lisboa, Portugal
King Faisal Specialist Hospital & Research Centre; Oncology
🇸🇦Riyadh, Saudi Arabia
Institute for Onc/Rad Serbia
🇷🇸Belgrade, Serbia
Institute of Oncology Ljubljana
🇸🇮Ljubljana, Slovenia
Clinica Universitaria de Navarra; Servicio de Oncologia
🇪🇸Pamplona, Navarra, Spain
Albert Schweitzer Ziekenhuis
🇳🇱Dordrecht, Netherlands
Świętokrzyskie Centrum Onkologii; Dział Chemioterapii
🇵🇱Kielce, Poland
Cent.Onkologii-Instytut im. M. S-Curie, Klinika Now. Piersi i Chirurgii Rekon
🇵🇱Warszawa, Poland
IPO de Coimbra; Servico de Oncologia Medica
🇵🇹Coimbra, Portugal
IPO do Porto; Servico de Oncologia Medica
🇵🇹Porto, Portugal
Hospital Pereira Rossell; Oncology Department
🇺🇾Montevideo, Uruguay
Hameed Latif Hospital; Department of Oncology
🇵🇰Lahore, Pakistan
Instituto;Oncologico Miraflores
🇵🇪Lima, Peru
Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii
🇵🇱Otwock, Poland
Hospital do Espirito Santo; Servico de Oncologia Medica
🇵🇹Evora, Portugal
Hospital Beatriz Angelo; Departamento de Oncologia
🇵🇹Loures, Portugal
Grupo Oncológico Cooperativo Uruguayo; Hospital de Clínicas - Dpto. de Oncología
🇺🇾Montevideo, Uruguay
Cross Cancer Institute ; Dept of Medical Oncology
🇨🇦Edmonton, Alberta, Canada
William Osler Health System Brampton Civic Hospital
🇨🇦Brampton, Ontario, Canada
El Mokatam HIO Hospital
🇪🇬Cairo, Egypt
Universitätsklinikum Hamburg-Eppendorf; Frauenklinik
🇩🇪Hamburg, Germany
Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia
🇪🇸Las Palmas de Gran Canaria, LAS Palmas, Spain
Hospital de Gran Canaria Dr. Negrin; Servicio de Oncologia
🇪🇸Las Palmas de Gran Canaria, LAS Palmas, Spain
Hospital Universitari Sant Joan de Reus; Servicio de Oncologia
🇪🇸Reus, Tarragona, Spain
Christie Hospital; Breast Cancer Research Office
🇬🇧Manchester, United Kingdom
Hospital Sao Jose
🇧🇷São Paulo, SP, Brazil
Jiangsu Cancer Hospital
🇨🇳Nanjing, China
Queen Elizabeth Hospital; Clinical Oncology
🇭🇰Hong Kong, Hong Kong