A Study to Evaluate Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT00567190
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This study was a Phase III, randomized, double-blind, placebo-controlled, multicenter international clinical trial conducted to investigate the use of pertuzumab in combination with trastuzumab and docetaxel as first-line treatment for participants with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Participants could have received one prior hormonal treatment for MBC. Participants may have received systemic breast cancer treatment in the neo-adjuvant or adjuvant setting, provided that the participant had experienced a disease-free interval (DFI) of greater than or equal to (≥)12 months from completion of adjuvant systemic treatment (excluding hormonal therapy) to metastatic diagnosis. Participants may have received trastuzumab and/or a taxane during the neo-adjuvant or adjuvant treatment.
Participants were randomized in 1:1 ratio to receive either pertuzumab or placebo, along with trastuzumab and docetaxel once every 3 weeks (q3w), during the treatment phase of the study until investigator-assessed radiographic or clinical progressive disease, unmanageable toxicity, or study termination. Participants in the Placebo arm were not allowed to receive open-label pertuzumab after discontinuation from study treatment. However, if any analysis of overall survival had met the predefined criteria for statistical significance, participants in the Placebo arm still on treatment were offered the option to receive open-label pertuzumab in addition to other study medications.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 808
- Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and candidate for chemotherapy. Participants with measurable and non-measurable disease are eligible (locally recurrent disease must not be amenable to resection with curative intent; participants with de novo Stage IV disease are eligible)
- Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC)
- Left ventricular ejection fraction (LVEF) ≥50 percent (%) at baseline (within 42 days of randomization)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective form of contraception and to continue its use for the duration of study treatment and for at least 7 months after the last dose of study treatment
- History of anti-cancer therapy for MBC (with the exception of one prior hormonal regimen for MBC, which must be stopped prior to randomization)
- History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting
- History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of less than (<)12 months
- History of persistent Grade ≥2 hematologic toxicity resulting from previous adjuvant therapy
- Current peripheral neuropathy of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0, Grade ≥3 at randomization
- History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent
- Current clinical or radiographic evidence of central nervous system (CNS) metastases
- Computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain is mandatory in cases of clinical suspicion of brain metastases
- History of exposure to cumulative doses of anthracyclines
- Current uncontrolled hypertension or unstable angina
- History of congestive heart failure (CHF) of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exception: atrial fibrillation or paroxysmal supraventricular tachycardia)
- History of myocardial infarction within 6 months of randomization
- History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
- Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
- Inadequate organ function, as defined in the protocol, within 28 days prior to randomization
- Current severe, uncontrolled systemic disease
- Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
- Pregnant or lactating women
- History of receiving any investigational treatment within 28 days of randomization
- Current known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
- Receipt of IV antibiotics for infection within 14 days of randomization
- Current chronic daily treatment with corticosteroids (excluding inhaled steroids)
- Known hypersensitivity to any of the study drugs
- Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Trastuzumab + Docetaxel Placebo Participants randomized to this arm received placebo IV q3w and trastuzumab 6 mg/kg IV q3w, plus docetaxel 75 mg/m\^2 IV q3w (for at least 6 cycles; 1 cycle was 21 days). After Cycle 6, continuation of docetaxel treatment was at the discretion of the participant and treating physician. Participants remained in the treatment phase of the study until investigator-assessed radiographic or clinical evidence of disease progression, unmanageable toxicity, or study termination and were followed for survival until death, loss to follow-up, withdrawal of consent, or study termination. Pertuzumab + Trastuzumab + Docetaxel Trastuzumab Participants randomized to this arm received pertuzumab 420 milligrams (mg) intravenously (IV) once every 3 weeks (q3w) and trastuzumab 6 milligrams per kilogram (mg/kg) IV q3w, plus docetaxel 75 milligrams per square metre of body surface (mg/m\^2) IV q3w (for at least 6 cycles; 1 cycle was 21 days). After Cycle 6, continuation of docetaxel treatment was at the discretion of the participant and treating physician. Participants remained in the treatment phase of the study until investigator-assessed radiographic or clinical evidence of disease progression, unmanageable toxicity, or study termination and were followed for survival until death, loss to follow-up, withdrawal of consent, or study termination. Pertuzumab + Trastuzumab + Docetaxel Pertuzumab Participants randomized to this arm received pertuzumab 420 milligrams (mg) intravenously (IV) once every 3 weeks (q3w) and trastuzumab 6 milligrams per kilogram (mg/kg) IV q3w, plus docetaxel 75 milligrams per square metre of body surface (mg/m\^2) IV q3w (for at least 6 cycles; 1 cycle was 21 days). After Cycle 6, continuation of docetaxel treatment was at the discretion of the participant and treating physician. Participants remained in the treatment phase of the study until investigator-assessed radiographic or clinical evidence of disease progression, unmanageable toxicity, or study termination and were followed for survival until death, loss to follow-up, withdrawal of consent, or study termination. Pertuzumab + Trastuzumab + Docetaxel Docetaxel Participants randomized to this arm received pertuzumab 420 milligrams (mg) intravenously (IV) once every 3 weeks (q3w) and trastuzumab 6 milligrams per kilogram (mg/kg) IV q3w, plus docetaxel 75 milligrams per square metre of body surface (mg/m\^2) IV q3w (for at least 6 cycles; 1 cycle was 21 days). After Cycle 6, continuation of docetaxel treatment was at the discretion of the participant and treating physician. Participants remained in the treatment phase of the study until investigator-assessed radiographic or clinical evidence of disease progression, unmanageable toxicity, or study termination and were followed for survival until death, loss to follow-up, withdrawal of consent, or study termination. Placebo + Trastuzumab + Docetaxel Trastuzumab Participants randomized to this arm received placebo IV q3w and trastuzumab 6 mg/kg IV q3w, plus docetaxel 75 mg/m\^2 IV q3w (for at least 6 cycles; 1 cycle was 21 days). After Cycle 6, continuation of docetaxel treatment was at the discretion of the participant and treating physician. Participants remained in the treatment phase of the study until investigator-assessed radiographic or clinical evidence of disease progression, unmanageable toxicity, or study termination and were followed for survival until death, loss to follow-up, withdrawal of consent, or study termination. Placebo + Trastuzumab + Docetaxel Docetaxel Participants randomized to this arm received placebo IV q3w and trastuzumab 6 mg/kg IV q3w, plus docetaxel 75 mg/m\^2 IV q3w (for at least 6 cycles; 1 cycle was 21 days). After Cycle 6, continuation of docetaxel treatment was at the discretion of the participant and treating physician. Participants remained in the treatment phase of the study until investigator-assessed radiographic or clinical evidence of disease progression, unmanageable toxicity, or study termination and were followed for survival until death, loss to follow-up, withdrawal of consent, or study termination.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Determined by an Independent Review Facility Tumor assessments every 9 weeks from randomization to IRF-determined PD or death from any cause, whichever occurred first, up to the primary completion date (up to 3 years, 3 months) PFS was defined as the time from randomization to first documented radiographical progressive disease (PD), as determined by an independent review facility (IRF) using RECIST version 1.0, or death from any cause (within 18 weeks of last tumor assessment), whichever occurred first (Kaplan-Meier method). For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum of the LD recorded since treatment started or the appearance of ≥1 new lesion. For non-target lesions, PD was defined as the appearance of ≥1 new lesion or unequivocal progression of existing lesions. Participants without IRF-determined PD or who had not died within 18 weeks of their last IRF-determined, progression-free tumor assessment were censored at the date of the last IRF-reviewed, evaluable tumor assessment; those with no post-baseline tumor assessment and who had not died within 18 weeks of baseline were censored at 1 day.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Determined by the Investigator Tumor assessments every 9 weeks from randomization to investigator-determined PD or death from any cause, whichever occurred first (median [range] time on study in pertuzumab vs. placebo arms: 201.8 [0.7-520.0] weeks vs. 138.0 [0.4-514.7] weeks) PFS was defined as the time from randomization to first documented radiographical progressive disease (PD), as determined by the investigator using RECIST version 1.0, or death from any cause (within 18 weeks of last tumor assessment), whichever occurred first (Kaplan-Meier method). For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum of the LD recorded since treatment started or the appearance of ≥1 new lesion. For non-target lesions, PD was defined as the appearance of ≥1 new lesion or unequivocal progression of existing lesions. Participants without PD or who had not died within 18 weeks of their last investigator-determined, progression-free tumor assessment were censored at the date of the last investigator tumor assessment; those with no post-baseline tumor assessment and who had not died within 18 weeks of baseline were censored at 1 day.
Duration of Objective Response Determined by an Independent Review Facility From initial IRF-confirmed objective response until IRF-determined progressive disease (PD), death, or first administration of next line of anti-cancer therapy (whichever occurred first), up to the primary completion date (up to 3 years, 3 months) Duration of objective response (estimated using the Kaplan-Meier method) was defined as the time from the initial confirmed complete response (CR) or partial response (PR), the date of tumor assessment at which the CR/PR was first detected by the independent review facility (IRF) using RECIST version 1.0, until the date of IRF-determined progressive disease (PD), death from any cause within 18 weeks of the last tumor assessment, or first administration of next line of anti-cancer therapy (whichever occurred first). If the visit when the initial CR or PR was observed spanned multiple dates, the latest date was used. Only participants in the ITT analysis population with an IRF-determined objective response (CR or PR), observed prior to IRF-assessed PD, death or next line of anti-cancer therapy, were included in the analysis. Participants who did not progress or die after they had a confirmed response were censored at the date of their last IRF-evaluable tumor measurement.
Time to Symptom Progression Every 9 weeks from Baseline until investigator-determined progressive disease, up to the primary completion date (up to 3 years, 3 months) Time to symptom progression was defined as the time from randomization to the first symptom progression as measured by the Functional Assessment of Cancer Therapy-for patients with Breast Cancer (FACT-B) questionnaire with the Trial Outcomes Index-Physical/Functional/Breast (TOI-PFB) subscale. The FACT-B TOI-PFB subscale contains 24 items from 3 subsections of the FACT-B questionnaire: Physical well-being, functional well-being, and additional concerns for breast cancer patients (breast cancer subscale \[BCS\]). All items in the questionnaire were rated by the patient on a 5-point scale ranging from 0 ("not at all") to 4 ("very much"). The total score ranged from 0 to 96. A higher score indicates better perceived quality of life. A positive change score from baseline indicates improvement. Symptom progression was defined as a decrease from baseline of 5 points or more.
Objective Response Determined by an Independent Review Facility Tumor assessments every 9 weeks from Baseline until IRF-determined progressive disease (PD), death, or first administration of next line of anti-cancer therapy (whichever occurred first), up to the primary completion date (up to 3 years, 3 months) An objective response was defined as the percentage of participants with confirmed best overall response of complete response (CR) or partial response (PR) determined by an independent review facility (IRF) using RECIST v1.0 on two consecutive occasions ≥4 weeks apart. For target lesions, CR: disappearance of all target lesions; PR: ≥30% decrease in the sum of the longest diameter (LD) of target lesions (baseline sum LD as reference); PD: ≥20% increase in the sum of the LD of target lesions (smallest sum of the LD recorded as reference) or appearance of ≥1 new lesion; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase for PD. For non-target lesions, CR: disappearance of all non-target lesions; Incomplete/SD: persistence of ≥1 non-target lesions; PD: unequivocal progression of existing non-target lesions. 95% confidence intervals (CI) were calculated only for clinical responses using the Pearson-Clopper method.
Overall Number of Participants Who Experienced at Least One Adverse Event, Including Serious and Non-Serious Adverse Events, by Most Severe Intensity (According to NCI-CTCAE v3.0) During the Treatment Period Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm) Adverse event (AE) severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v3.0); if the AE was not specifically listed, the following grades of severity were used: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening or disabling; and Grade 5 = death. Severe and serious are not synonymous. Severity refers to the intensity of an AE, whereas a serious AE must meet criteria set out in the protocol; both were independently assessed for each AE. Only the most severe intensity was counted for multiple occurrences of the same AE in one participant. AEs reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants who crossed over from placebo to pertuzumab. Median \[range\] time on study treatment per arm: Placebo: 49.3 \[0.3-514.7\] weeks; Pertuzumab: 75.7 \[0.6-519.6\] weeks; Crossover: 129.9 \[0.3-322.3\] weeks.
Overall Survival From randomization to death from any cause, up to each respective analysis data cut-off date (see the Description field for the median time on study per treatment arm) Overall survival (OS) was the time from randomization to death from any cause, using Kaplan-Meier methodology. Survival data was collected every 18 weeks during the post-treatment follow-up period until death, loss to follow-up, or withdrawal of consent. Those who were alive, lost to follow up, or withdrew consent were censored at the latest date they participated in the study; those without post-baseline data were censored at 1 day. OS analyses were planned to take place at the primary completion date (First Interim), after 385 deaths (Event-Driven Final), and at the end of study (End-of-Study). A second interim OS analysis was planned due to a formal request from the European Medicines Agency. Median \[range\] time in weeks on study at each OS analysis (Pertuzumab vs. Placebo): First: 77.1 \[0.7-165.3\] vs. 73.1 \[0.4-165.3\]; Second: 117.1 \[0.7-207.9\] vs. 105.9 \[0.4-207.9\]; Event-Driven Final: 189.9 \[0.7-304.1\] vs. 140.5 \[0.4-301.6\]; End-of-Study: 201.8 \[0.7-520.0\] vs. 138.0 \[0.4-514.7\].
Overall Number of Adverse Events by Severity (NCI-CTCAE v3.0 All Grades and Grades 3 to 5) Per 100 Patient-Years of Exposure During the Treatment Period From Baseline to 42 days after the last dose of study treatment (total patient-years of exposure on study treatment in Placebo vs. Pertuzumab arms: 526.81 vs. 989.88 patient-years) Adverse event (AE) severity, including serious and non-serious AEs, was assessed according to the NCI-CTCAE version 3.0; if the AE was not specifically listed, the following grades of severity were used: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe; Grade 4 is life-threatening or disabling; and Grade 5 is death. Multiple occurrences of the same AE in 1 participant were counted multiple times. Only AEs that started during the overall study treatment period were included. The cutoff date for inclusion of events and for calculation of patient-years was the date of the most recent follow-up of the participant, defined as the last available date during the treatment period, excluding pre-treatment and safety follow-up data. Confidence intervals were calculated assuming the number of events followed a Poisson distribution. Data reported prior to the date of first crossover treatment were included under the Placebo arm for participants who crossed over from placebo to pertuzumab.
Cardiac-Related AEs to Monitor: Number of Participants Who Experienced at Least One Symptomatic Left Ventricular Dysfunction (LVD), Any LVD, or Serious AE Suggestive of Congestive Heart Failure by Severity During the Treatment Period Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm) Cardiac-related adverse events (AEs) to monitor during the study included investigator-assessed symptomatic left ventricular dysfunction (LVD), any LVD, or a serious adverse event (SAE) suggestive of congestive heart failure (CHF). All cardiac-related AEs were graded for severity according to NCI-CTCAE v3.0. Asymptomatic (Grades 1-2) and symptomatic (Grades 3-5) left ventricular systolic dysfunction (LVSD) both coded to the MedDRA preferred term LVD. Investigator-assessed events of symptomatic LVD were also graded for severity of symptoms according to Classes I (least severe) to IV (most severe) of the New York Heart Association (NYHA) Classification. SAEs suggestive of CHF were identified as serious events from the Standardized MedDRA Query (SMQ) (Wide) 'Cardiac Failure'. Median \[range\] time on study treatment per arm: Placebo: 49.3 \[0.3-514.7\] weeks; Pertuzumab: 75.7 \[0.6-519.6\] weeks; Crossover: 129.9 \[0.3-322.3\] weeks.
Number of Participants Who Experienced at Least One Adverse Event During the Post-Treatment Follow-Up Period From Day 43 after discontinuation of all study medication to end of post-treatment follow-up period (up to 3 years) The post-treatment period was defined as the period following the treatment discontinuation visit. Only the following new adverse events (AEs) should have been reported during the post-treatment follow-up period: 1. Cardiac events (regardless of causality or seriousness) that started up to 1 year after the last dose, except for symptomatic left ventricular systolic dysfunction (regardless of causality) that started up to 3 years after the last dose; and 2. Treatment-related serious AEs, regardless of start date. AEs are listed by Medical Dictionary for Regulatory Activities, Version 21.1 (MedDRA v21.1) System Organ Class (SOC) and Preferred Term (PT); PTs fall under the SOC that is listed immediately above it in the table. Multiple occurrences of the same AE in one participant was counted only once. AEs reported prior to first crossover treatment were included in the Placebo arm, and after that date in the Crossover arm, for participants who crossed over from placebo to pertuzumab.
Baseline LVEF Value and Change in LVEF From Baseline at Maximum Absolute Decrease Value During the Treatment Period Every 9 weeks from the date of randomization until Treatment Discontinuation Visit (median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks) All participants were required to have a left ventricular ejection fraction (LVEF) ≥50% at baseline, as measured by echocardiogram (preferred) or multiple-gated acquisition (MUGA) scan. The same method of LVEF assessment and the same institution/facility used at baseline was used throughout the study, to the extent possible. The baseline value was defined as the last valid value recorded during the pre-treatment period before or on study Day 1. The maximum absolute decrease in LVEF value was defined as the lowest post-baseline value up to the end of the overall study treatment period. Only data reported prior to the date of first crossover treatment were included for participants who crossed over from placebo to pertuzumab.
Number of Participants With Laboratory Abnormalities in Hematology Tests by Highest Grade According to NCI-CTCAE v3.0 During the Treatment Period On Day 1 (and Day 8 for some measures) of every treatment cycle (1 cycle is 21 days) until Treatment Discontinuation Visit (see Description for time on study treatment per arm) Clinical laboratory tests for hematology parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest grade according to NCI-CTCAE v3.0. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. Median \[range\] time on study treatment per arm: Placebo: 49.3 \[0.3-514.7\] weeks; Pertuzumab: 75.7 \[0.6-519.6\] weeks; Crossover: 129.9 \[0.3-322.3\] weeks. INR = International Normalized Ratio; PTT = partial thromboplastin time; WBC = white blood cell
Number of Participants Who Experienced at Least One Adverse Event to Monitor (Excluding Cardiac-Related AEs) by Severity During the Treatment Period Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm) The clinical diagnoses listed in this table, excluding cardiac safety (summarized separately), were also selected as adverse events (AEs) to monitor based on clinical and nonclinical data for pertuzumab and the safety profile established for trastuzumab, monoclonal antibodies in general, and potential effects associated with HER receptor inhibition. Search strategies were defined by single or aggregate MedDRA Preferred Terms (PT) through Standardized MedDRA Queries (SMQ), where possible, or based on Roche AE Group Terms (AEGT). Diarrhoea AEs: High-Level Term (HLT) 'Diarrhoea (excl. infective)' and PT 'Diarrhoea infectious'. Leukopenic and Febrile Neutropenic Infections: AEs from 'Infections \& Infestations' with start ≤14 days after start date of Grade ≥3 AEs in SMQ(narrow) 'Leukopenia' or PT 'Febrile neutropenia', respectively. Median \[range\] time on study treatment per arm: Placebo: 49.3 \[0.3-514.7\] weeks; Pertuzumab: 75.7 \[0.6-519.6\] weeks; Crossover: 129.9 \[0.3-322.3\] weeks.
Overall Number of Participants Who Experienced at Least One Adverse Event Leading to Discontinuation of Any or All Study Medication Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm) Participants could continue study treatment with pertuzumab/placebo plus trastuzumab when docetaxel was discontinued due to an adverse event (AE). Discontinuation of pertuzumab/placebo or trastuzumab due to an AE led to discontinuation of all study medication. The number of participants who discontinued any study medication due to an AE includes those who discontinued all study medication and those who discontinued docetaxel only and then continued on targeted therapy (note: some of these participants may have subsequently discontinued all treatment due to a separate AE). Multiple occurrences of the same adverse event in 1 participant was counted only once. AEs reported prior to first crossover treatment were included in the Placebo arm, and after that date in the Crossover arm, for those who crossed over from placebo to pertuzumab. Median \[range\] time on study treatment per arm: Placebo: 49.3 \[0.3-514.7\] weeks; Pertuzumab: 75.7 \[0.6-519.6\] weeks; Crossover: 129.9 \[0.3-322.3\] weeks.
Overall Number of Participants Who Experienced at Least One Adverse Event That Resulted in Interruption or Modification of Any Study Medication Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm) Pertuzumab, trastuzumab, and docetaxel administration could have been delayed to assess or treat adverse events (AEs). Docetaxel dose reduction was allowed for myelosuppression, hepatic dysfunction, and other toxicities. No dose reduction was allowed for pertuzumab or trastuzumab. Multiple occurrences of the same adverse event in one participant was counted only once. AEs reported prior to first crossover treatment were included in the Placebo arm, and after that date in the Crossover arm, for participants who crossed over from placebo to pertuzumab. Median \[range\] time on study treatment per arm: Placebo: 49.3 \[0.3-514.7\] weeks; Pertuzumab: 75.7 \[0.6-519.6\] weeks; Crossover: 129.9 \[0.3-322.3\] weeks
Number of Participants by Categories for the Maximum Absolute Decrease From Baseline in LVEF Value During the Treatment Period Every 9 weeks from the date of randomization until Treatment Discontinuation Visit (see Description for time on study treatment per arm) All participants were required to have an left ventricular ejection fraction (LVEF) ≥50% at baseline, as measured by echocardiogram (preferred) or multiple-gated acquisition (MUGA) scan. The same method of LVEF assessment and the same institution/facility used at baseline was used throughout the study, to the extent possible. The baseline value was defined as the last valid value recorded during the pre-treatment period before or on study Day 1. The maximum absolute decrease in LVEF value was defined as the lowest post-baseline value up to the end of the overall study treatment period. Data reported prior to first crossover treatment were included in the Placebo arm, and after that date in the Crossover arm, for participants who crossed over from placebo to pertuzumab. Median \[range\] time on study treatment per arm: Placebo: 49.3 \[0.3-514.7\] weeks; Pertuzumab: 75.7 \[0.6-519.6\] weeks; Crossover: 129.9 \[0.3-322.3\] weeks.
Number of Participants With Laboratory Abnormalities in Blood Biochemistry Tests by Highest Grade According to NCI-CTCAE v3.0 During the Treatment Period On Day 1 of every treatment cycle (1 cycle is 21 days) until Treatment Discontinuation Visit (see Description for time on study treatment per arm) Clinical laboratory tests for blood biochemistry parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest grade according to NCI-CTCAE v3.0. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. Median \[range\] time on study treatment per arm: Placebo: 49.3 \[0.3-514.7\] weeks; Pertuzumab: 75.7 \[0.6-519.6\] weeks; Crossover: 129.9 \[0.3-322.3\] weeks. ALP = alkaline phosphatase; GGT = gamma-glutamyl transferase; SGOT = serum glutamic-oxaloacetic transaminase; SGPT = serum glutamic-pyruvic transaminase
Trial Locations
- Locations (315)
UCLA
🇺🇸Los Angeles, California, United States
LAC USC Medical Center
🇺🇸Los Angeles, California, United States
St. Barnabas Cancer Center
🇺🇸Livingston, New Jersey, United States
Memorial City-Main Office
🇺🇸Houston, Texas, United States
Pacific Cancer Medical Center
🇺🇸Anaheim, California, United States
Central Hematology Oncology Medical Group Inc.
🇺🇸Alhambra, California, United States
Comprehensive Blood/Cancer Ctr
🇺🇸Bakersfield, California, United States
Kaiser Permanente - Baldwin Park
🇺🇸Baldwin Park, California, United States
Tower Cancer Research Foundation
🇺🇸Beverly Hills, California, United States
South Bay Oncology Hematology Partners
🇺🇸Campbell, California, United States
Wilshire Oncology Medical Group
🇺🇸West Covina, California, United States
Compassionate Cancer Care
🇺🇸Fountain Valley, California, United States
Pacific Coast Hematology/Oncology Medical Group
🇺🇸Fountain Valley, California, United States
St. Jude Heritage Healthcare; Virgiia K.Crosson Can Ctr
🇺🇸Fullerton, California, United States
TORI Central Administration
🇺🇸Los Angeles, California, United States
Wilshire Onc Med Grp., Inc
🇺🇸Glendora, California, United States
Cedars- Sinai Medical Center
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center Clin Lab
🇺🇸Los Angeles, California, United States
UCLA Hematology / Oncology Clinic
🇺🇸Los Angeles, California, United States
UCLA Med Ctr; Pharma Svcs
🇺🇸Los Angeles, California, United States
Sutter Gould Medical Foundation; Clinical Research
🇺🇸Modesto, California, United States
Kaiser Permanente - Oakland
🇺🇸Oakland, California, United States
UCLA Healthcare/Pasadena Oncology
🇺🇸Pasadena, California, United States
Bay Area Cancer Research Group, LLC
🇺🇸Pleasant Hill, California, United States
Ventura County Hematology-Oncology Specialists
🇺🇸Oxnard, California, United States
Sansum Santa Barbara Medical Foundation Clinic
🇺🇸Santa Barbara, California, United States
Santa Barbara Hematology Oncology Medical Group, Inc.
🇺🇸Santa Barbara, California, United States
Kaiser Permanente - Vallejo
🇺🇸Vallejo, California, United States
UCLA Hematology/Oncology
🇺🇸Santa Monica, California, United States
UCLA / Santa Clarita Valley Cancer Center
🇺🇸Valencia, California, United States
K. Permanente - Walnut Creek
🇺🇸Walnut Creek, California, United States
Innovative clinical research institute/American institute of research
🇺🇸Whittier, California, United States
MedStar Washington Hosp Center
🇺🇸Washington, District of Columbia, United States
Boca Raton Comprehensive Cancer Center
🇺🇸Boca Raton, Florida, United States
Florida Cancer Specialists -Cape Coral (Cape Coral Pkwy)
🇺🇸Cape Coral, Florida, United States
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
Florida Cancer Specialists - Cape Coral (Del Prado Blvd)
🇺🇸Cape Coral, Florida, United States
Northwest Oncology/ Hematology Assoc.
🇺🇸Coral Springs, Florida, United States
Florida Cancer Specialists; SCRI
🇺🇸Fort Myers, Florida, United States
UM Sylvester Deerfield Beach; Sylvester Cancer Ctr
🇺🇸Deerfield Beach, Florida, United States
Florida Cancer Specialists - Fort Myers (New Hampshire Ct)
🇺🇸Fort Myers, Florida, United States
Florida Cancer Specialists - Englewood
🇺🇸Englewood, Florida, United States
Florida Cancer Specialists - Broadway
🇺🇸Fort Myers, Florida, United States
Memorial Cancer Institute
🇺🇸Hollywood, Florida, United States
Lakeland Regional Cancer Center
🇺🇸Lakeland, Florida, United States
Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
Florida Cancer Specialists - Goodlette, Naples
🇺🇸Naples, Florida, United States
Florida Cancer Specialists - Pine Ridge, Naples
🇺🇸Naples, Florida, United States
Breast Cancer Centre at Memorial Hospital West
🇺🇸Pembroke Pines, Florida, United States
Florida Cancer Specialists - Port Charlotte
🇺🇸Port Charlotte, Florida, United States
Florida Cancer Specialists; Sarasota
🇺🇸Sarasota, Florida, United States
Florida Cancer Specialists - Sunset Lake, Venice
🇺🇸Venice, Florida, United States
Florida Cancer Specialists - Venice (S. Tamiami Tr)
🇺🇸Venice, Florida, United States
Northeast Georgia Medical Center; Oncology Research Dept-5C
🇺🇸Gainesville, Georgia, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Central Georgia Hematology Oncology Associates
🇺🇸Macon, Georgia, United States
Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital
🇺🇸Marietta, Georgia, United States
Central GA Cancer Care
🇺🇸Warner Robins, Georgia, United States
Elmhurst Hospital
🇺🇸Elmhurst, Illinois, United States
Hematology Oncology Consultants Ltd
🇺🇸Naperville, Illinois, United States
Quincy Medical Group
🇺🇸Quincy, Illinois, United States
Midwestern Regional Medical Center; Office of Research
🇺🇸Zion, Illinois, United States
Monroe Medical Associates - Hobart
🇺🇸Hobart, Indiana, United States
St. Mary Medical Center
🇺🇸Walla Walla, Washington, United States
Community Hospital; Pharmacy
🇺🇸Munster, Indiana, United States
Northwest Oncology
🇺🇸Munster, Indiana, United States
Monroe Medical Associates
🇺🇸Munster, Indiana, United States
Uni of Iowa Hospital&Clinic; Holden Comprehens. Cancer Ctr
🇺🇸Iowa City, Iowa, United States
Family Medicine Vincennes
🇺🇸Vincennes, Indiana, United States
University of Kansas; Medical Center & Medical pavilion
🇺🇸Westwood, Kansas, United States
Christus Schumpert Health System
🇺🇸Shreveport, Louisiana, United States
Southdale Cancer Clinic U of M Medical Center, Fairview- Edina
🇺🇸Edina, Minnesota, United States
The Jones Clinic, PC
🇺🇸New Albany, Mississippi, United States
Southeast Nebraska Cancer Center;; Southeast Nebraska Hematology and Oncology
🇺🇸Lincoln, Nebraska, United States
Norfolk Oncology Consultants
🇺🇸Norfolk, Nebraska, United States
San Juan Oncology Associates
🇺🇸Farmington, New Mexico, United States
Canandaigua-Interlakes Found
🇺🇸Canandaigua, New York, United States
Brockport-Interlakes Foundation
🇺🇸Brockport, New York, United States
Geneva-Interlakes Foundation
🇺🇸Geneva, New York, United States
ProHEALTH Care Associates LLP
🇺🇸Lake Success, New York, United States
Beth Israel Comprehensive Cancer Center Pharmacy
🇺🇸New York, New York, United States
The Women'sOncology & Wellness Practice
🇺🇸New York, New York, United States
Carolina Oncology Specialists, PA - Hickory
🇺🇸Hickory, North Carolina, United States
Carolina BioOncology Institute, PLCC
🇺🇸Huntersville, North Carolina, United States
NW Carolina Onc & Hem
🇺🇸Lenoir, North Carolina, United States
Gabrail Cancer Center
🇺🇸Dover, Ohio, United States
Hema Onc Conslts-Grant Ave
🇺🇸Columbus, Ohio, United States
The Mark H. Zangmeister Ctr; Mid Ohio Onc/Hem Inc.
🇺🇸Columbus, Ohio, United States
Hematology Onc Consultants
🇺🇸Columbus, Ohio, United States
Cancer Care Assoc-S. Ingo
🇺🇸Tulsa, Oklahoma, United States
Hematology Oncology Consultants (NWK)
🇺🇸Granville, Ohio, United States
Medical College of Ohio; Cancer Institute
🇺🇸Toledo, Ohio, United States
CA Care Associates-OK Oncology and Hematology
🇺🇸Tulsa, Oklahoma, United States
OK Oncology & Hematology PC
🇺🇸Tulsa, Oklahoma, United States
Cons in Med Onc and Hem
🇺🇸Darby, Pennsylvania, United States
Consultants Med Onc & Hem
🇺🇸Ridley Park, Pennsylvania, United States
Uni of Pittsburgh; Magee-Women'S Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Consultants in Medical Oncology/Hematology
🇺🇸Drexel Hill, Pennsylvania, United States
Conslts in Med Onc (Newtown); Bryn Mawr Health Canc Ctr
🇺🇸Newtown Square, Pennsylvania, United States
Armstrong County Memorial Hospital
🇺🇸Kittanning, Pennsylvania, United States
Erlanger Health System; Oncology Research
🇺🇸Chattanooga, Tennessee, United States
McLeod Cancer and Blood Center
🇺🇸Johnson City, Tennessee, United States
Park Plaza
🇺🇸Houston, Texas, United States
St. Joseph's
🇺🇸Houston, Texas, United States
Willowbrook
🇺🇸Houston, Texas, United States
Oncology Consultants
🇺🇸Houston, Texas, United States
St. Luke's
🇺🇸Houston, Texas, United States
Katy-Christus St. Catherine
🇺🇸Katy, Texas, United States
Oncology Consultants - Sugar Land
🇺🇸Sugar Land, Texas, United States
Northern Utah Associates
🇺🇸Ogden, Utah, United States
Sanatorio Güemes; Oncología
🇦🇷Buenos Aires, Argentina
Northwest Medical Specialties
🇺🇸Tacoma, Washington, United States
Wellmonth Physician Services
🇺🇸Bristol, Virginia, United States
Centro de Oncologia e Investigacion Buenos Aires (COIBA)
🇦🇷Buenos Aires, Argentina
Instituto Medico Especializado (IME); Oncologia
🇦🇷Caba, Argentina
Center Instituto Médico Privado I.M.P.; Oncology
🇦🇷Chaco-resistencia, Argentina
Policlinica Privada Site la Plata SA; Oncology
🇦🇷La Plata, Argentina
Unidad Oncológica De Neuquén
🇦🇷Neuquén, Argentina
Hosp Provincial D. Centenarios; Oncology Dept
🇦🇷Rosario, Argentina
Crio - Centro Regional Integrado de Oncologia
🇧🇷Fortaleza, CE, Brazil
Clinica Amo - Assistencia Medica Em Oncologia
🇧🇷Salvador, BA, Brazil
Centro Goiano de Oncologia - CGO
🇧🇷Goiania, GO, Brazil
Hospital Universitario Clementino Fraga Filho - UFRJ; Oncologia
🇧🇷Rio de Janeiro, RJ, Brazil
Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, RS, Brazil
Hospital das Clinicas - UFRGS
🇧🇷Porto Alegre, RS, Brazil
Hospital Nossa Senhora da Conceicao
🇧🇷Porto Alegre, RS, Brazil
Hospital Amaral Carvalho
🇧🇷Jau, SP, Brazil
Hospital das Clinicas - FMUSP Ribeirao Preto
🇧🇷Ribeirao Preto, SP, Brazil
Faculdade de Medicina do ABC - FMABC; Oncologia e Hematologia
🇧🇷Santo Andre, SP, Brazil
Instituto do Cancer Arnaldo Vieira de Carvalho - ICAVC; Pesquisa Clinica
🇧🇷Sao Paulo, SP, Brazil
Iso - Inst. Santista de Oncologia
🇧🇷Santos, SP, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, SP, Brazil
Inst. Brasileiro de Controle Ao Cancer; Oncologia Clinica / Quimioterapia
🇧🇷Sao Paulo, SP, Brazil
St. Michael'S Hospital
🇨🇦Toronto, Ontario, Canada
Instituto de Oncologia de Sorocaba - CEPOS
🇧🇷Sorocaba, SP, Brazil
Shanghai First People's Hospital
🇨🇳Shanghai, China
Hospital Cima San Jose; Oncology
🇨🇷San Jose, Costa Rica
Clinical Hospital Sisters of Mercy
🇭🇷Zagreb, Croatia
University Hospital Centre Zagreb; Clinic For Oncology
🇭🇷Zagreb, Croatia
Teodoro Maldonado Carbo Hospital; Oncology Service
🇪🇨Guayaquil, Ecuador
Hospital Carlos Andrade Marin; Servicio de Oncología
🇪🇨Quito, Ecuador
Tampere University Hospital; Dept of Oncology
🇫🇮Tampere, Finland
Centre Oncologie Du Pays Basque
🇫🇷Bayonne, France
Clinique Tivoli; Sce Radiotherapie
🇫🇷Bordeaux, France
Centre Georges Francois Leclerc; Oncologie 3
🇫🇷Dijon, France
Centre Hospitalier Departemental Les Oudairies
🇫🇷La Roche Sur Yon, France
Centre Jean Bernard
🇫🇷Le Mans, France
Centre Antoine Lacassagne; Hopital De Jour A2
🇫🇷Nice, France
Ico Rene Gauducheau; Oncologie
🇫🇷Saint Herblain, France
Groupe Hospitalier Sud; Oncologie Radiotherapie
🇫🇷Salouel, France
Onkologische Schwerpunktpraxis Bielefeld; Haemotologie & Internistische onkologie
🇩🇪Bielefeld, Germany
Onkologischer Schwerpunkt am Oskar-Helene-Heim; Dres. Herrenberger, Keitel-Wittig u. Kirsch
🇩🇪Berlin, Germany
Universitätsklinikum Essen; Zentrum Für Frauenheilkunde
🇩🇪Essen, Germany
Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie
🇩🇪Halle, Germany
Universitätsklinikum Hamburg-Eppendorf; Frauenklinik
🇩🇪Hamburg, Germany
Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
🇩🇪Heidelberg, Germany
Krankenhaus Rheinfelden; Frauenklinik
🇩🇪Rheinfelden, Germany
St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe
🇩🇪Koeln, Germany
Universitätsmedizin Mainz; Klinik u. Poliklinik f. Geburtshilfe u. Frauenheilkunde
🇩🇪Mainz, Germany
Robert-Bosch-Krankenhaus; Hämatologie, Onkologie und Palliativmedizin
🇩🇪Stuttgart, Germany
Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie
🇩🇪Trier, Germany
Universitätsklinik Tübingen; Frauenklinik
🇩🇪Tübingen, Germany
Therapeutic Research Inst. & Lab S.A. (Trial)
🇬🇹Guatemala City, Guatemala
Grupo Angeles
🇬🇹Guatemala City, Guatemala
Haematologisch-Onkologische Praxis; Dr. med. Christoph Maintz und Matthias Groschek
🇩🇪Wuerselen, Germany
Centro Oncologico S.A.
🇬🇹Guatemala, Guatemala
Prince of Wales Hosp; Dept. Of Clinical Onc
🇭🇰Shatin, Hong Kong
Ospedale Antonio Perrino; Oncologia Medica
🇮🇹Brindisi, Puglia, Italy
Chiba Cancer Center; Breast Surgical Oncology
🇯🇵Chiba, Japan
Ospedale Misericordia E Dolce; Oncologia Medica
🇮🇹Prato, Toscana, Italy
Aichi Cancer Center Hospital, Breast Oncology
🇯🇵Aichi, Japan
Natl Hosp Org Shikoku; Cancer Ctr, Surgery
🇯🇵Ehime, Japan
National Cancer Center Hospital East; Breast and Medical Oncology
🇯🇵Chiba, Japan
Kitakyushu Municipal Medical Center, Surgery
🇯🇵Fukuoka, Japan
National Hospital Organization Kyushu Cancer Center;Breast Oncology
🇯🇵Fukuoka, Japan
Iwate Med Univ School of Med; Surgery
🇯🇵Iwate, Japan
Sagara Hospital; Breast Surgery
🇯🇵Kagoshima, Japan
Gunma University Hospital; Department of Thoracic and Visceral Organ Surgery
🇯🇵Gunma, Japan
St. Marianna University School of Medicine Hospital, Breast and Endocrine Surgery
🇯🇵Kanagawa, Japan
Tokai University Hospital, Breast and Endocrine Surgery
🇯🇵Kanagawa, Japan
Kumamoto City Hospital, Breast and Endocrine Surgery
🇯🇵Kumamoto, Japan
Kyoto University Hospital; Breast Surgery
🇯🇵Kyoto, Japan
Niigata Cancer Ctr Hospital; Breast Surgery
🇯🇵Niigata, Japan
OSAKA CITY GENERAL HOSPITAL;Medical Oncology
🇯🇵Osaka, Japan
Osaka University Hospital; Breast and Endocrine Surgery
🇯🇵Osaka, Japan
Saitama Medical University International Medical Center; Medical Oncology
🇯🇵Saitama, Japan
Shizuoka General Hospital; Breast Surgery
🇯🇵Shizuoka, Japan
Jichi Medical University; Dept of Clinical Oncology
🇯🇵Tochigi, Japan
National Cancer Center Hospital; Breast and Medical Oncology
🇯🇵Tokyo, Japan
St. Luke's Internat. Hospital, Breast Surgical Oncology
🇯🇵Tokyo, Japan
Tokyo Metropolitan; Komagome Hospital, Surgery
🇯🇵Tokyo, Japan
Tokyo Medical Uni. Hospital; Breast Oncology
🇯🇵Tokyo, Japan
Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
🇰🇷Seoul, Korea, Republic of
National Cancer Center; Medical Oncology
🇰🇷Gyeonggi-do, Korea, Republic of
Daugavpils Regional Hospital
🇱🇻Daugavpils, Latvia
Samsung Medical Centre; Division of Hematology/Oncology
🇰🇷Seoul, Korea, Republic of
Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.
🇰🇷Seoul, Korea, Republic of
Asan Medical Center, Uni Ulsan Collegemedicine; Dept.Internal Medicine / Divisionhematology/Oncology
🇰🇷Seoul, Korea, Republic of
Rigas Austrumu Kliniska Universitates slimnica, Latvijas Onkologijas centrs
🇱🇻Riga, Latvia
Hospital Angeles Metropolitano; Room 220
🇲🇽Mexico City, Mexico CITY (federal District), Mexico
P.Stradins Clinical University Hospital, Oncology Centre
🇱🇻Riga, Latvia
Centro Oncologico Estatal ISSEMYM
🇲🇽Toluca, Mexico
Clinical Hospital; Oncology Department
🇲🇰Bitola, North Macedonia
Institute of Radiotherapy Oncology
🇲🇰Skopje, North Macedonia
Private Health Organization Acibadem Sistina Hospital
🇲🇰Skopje, North Macedonia
Cebu Cancer Institute; Perpetual Succour Hospital
🇵🇭Cebu City, Philippines
Veterans Memorial Medical Center; Oncology
🇵🇭Quezon City, Philippines
St Luke'S Medical Centre; Oncology
🇵🇭Quezon City, Philippines
Samodzielny Publiczny Kliniczny Nr 1 W Lublinie; Klinika Chirurgii Onkologicznej
🇵🇱Lublin, Poland
COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
🇵🇱Lublin, Poland
Oddzial Chemioterapii Szpitala Klinicznego Nr 1 w Poznaniu
🇵🇱Poznan, Poland
Zachodniopomorskie Centrum Onkologii, Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych
🇵🇱Szczecin, Poland
Regional Oncology Hospital Of Kursk; Chemotherapy
🇷🇺Kislino, Kursk Region, Russian Federation
Blokhin Cancer Research Center; Combined Treatment
🇷🇺Moscow, Russian Federation
Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy
🇷🇺Moscow, Russian Federation
State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis
🇷🇺Orenburg, Russian Federation
Omsk Region Clinical Oncology Dispensary; 1St Sergical Department
🇷🇺Omsk, Russian Federation
SBI of Healthcare Samara Regional Clinical Oncology Dispensary
🇷🇺Samara, Russian Federation
SBI of Healthcare Leningrad Regional Oncology Dispensary
🇷🇺St Petersburg, Russian Federation
National University Hospital; National University Cancer Institute, Singapore (NCIS)
🇸🇬Singapore, Singapore
National Cancer Centre; Medical Oncology
🇸🇬Singapore, Singapore
Hospital Univ Vall d'Hebron; Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital Universitario de Canarias;servicio de Oncologia
🇪🇸La Laguna, Tenerife, Spain
Centro Oncologico MD Anderson Internacional; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia
🇪🇸Lerida, Spain
Hospital Duran i Reynals; Oncologia
🇪🇸Barcelona, Spain
Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia
🇪🇸Jaen, Spain
Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología
🇪🇸La Coruña, Spain
Hospital Universitario 12 de Octubre; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
🇪🇸Malaga, Spain
Chulalongkorn Hospital; Medical Oncology
🇹🇭Bangkok, Thailand
National Cancer Inst.
🇹🇭Bangkok, Thailand
Rajavithi Hospital; Division of Medical Oncology
🇹🇭Bangkok, Thailand
Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
🇹🇭Bangkok, Thailand
Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
🇹🇭Bangkok, Thailand
Broomfield Hospital; Oncology
🇬🇧Chelmsford, United Kingdom
Songklanagarind Hospital; Department of Oncology
🇹🇭Songkhla, Thailand
St James Uni Hospital; Icrf Cancer Medicine Research Unit
🇬🇧Leeds, United Kingdom
Leicester Royal Infirmary; Dept. of Medical Oncology
🇬🇧Leicester, United Kingdom
Mount Vernon Hospital; Centre For Cancer Treatment
🇬🇧Northwood, United Kingdom
Royal Free Hospital; Dept of Oncology
🇬🇧London, United Kingdom
Charing Cross Hospital; Medical Oncology.
🇬🇧London, United Kingdom
Royal Cornwall Hospital; Dept of Clinical Oncology
🇬🇧Truro, United Kingdom
The Clatterbridge Cancer Ctr For Oncolgy
🇬🇧Wirral, United Kingdom
Southend Hospital; Oncology Dept
🇬🇧Westcliffe-on-sea, United Kingdom
Jilin Cancer Hospital
🇨🇳Changchun, China
Fuzhou General Hospital, PLA Nanjing Military Area Command
🇨🇳Fuzhou, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai City, China
Southwest
🇺🇸Houston, Texas, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Kaiser Permanente San Diego; Hepatology Research
🇺🇸San Diego, California, United States
K. Permanente - San Fransisco
🇺🇸San Francisco, California, United States
Jackson Memorial Hospital
🇺🇸Miami, Florida, United States
University of Miami School of Medicine
🇺🇸Miami, Florida, United States
Hematology-Oncology of Indiana, Pc
🇺🇸Indianapolis, Indiana, United States
Minneapolis Oncology Hamatology PA
🇺🇸Minneapolis, Minnesota, United States
US Oncology Research at Minnesota Oncology
🇺🇸Minneapolis, Minnesota, United States
Mercy Physicians of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Oncology Hematology Care Inc
🇺🇸Cincinnati, Ohio, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
🇺🇸Nashville, Tennessee, United States
South Texas Oncology Hematology
🇺🇸San Antonio, Texas, United States
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
🇮🇹Meldola, Emilia-Romagna, Italy
Ospedale Provinciale Santa Maria delle Croci
🇮🇹Ravenna, Emilia-Romagna, Italy
Az. Osp. Spedali Civili; Divisione Di Oncologia - Iii Medicina
🇮🇹Brescia, Lombardia, Italy
Fondazione Del Piemonte Per L'oncologia IRCC Di Candiolo
🇮🇹Candiolo, Piemonte, Italy
Azienda Sanitaria S. Maria Annunziata; S. C. Oncologia Medica
🇮🇹Antella (FI), Toscana, Italy
Community Cancer Center Rutland Regional Medical Center
🇺🇸Rutland, Vermont, United States
St. Bartholomew'S Hospital; Dept of Medical Oncology
🇬🇧London, United Kingdom
St George'S Hospital; Oncology Research Office /Oncology Opd
🇬🇧London, United Kingdom
Instituto Nacional de Cancer - INCa; Oncologia
🇧🇷Rio de Janeiro, RJ, Brazil
Hospital de Caridade de Ijui; Oncologia
🇧🇷Ijui, RS, Brazil
Hospital Perola Byington
🇧🇷Sao Paulo, SP, Brazil
Hospital Estadual do Servidor Publico
🇧🇷Sao Paulo, SP, Brazil
K. Permanente - San Jose
🇺🇸San Jose, California, United States
Florida Cancer Specialists-Broadway, Fort Myers
🇺🇸Fort Myers, Florida, United States
Private Practice- Carolyn Hendricks, MD
🇺🇸Bethesda, Maryland, United States
Hematology-Oncology Consultants, Pc
🇺🇸Omaha, Nebraska, United States
UC Davis Cancer Center; Oncology
🇺🇸Sacramento, California, United States
Bay Area Oncology
🇺🇸Tampa, Florida, United States
Private Practice
🇺🇸Orlando, Florida, United States
Jewish Cancer Care
🇺🇸Louisville, Kentucky, United States
Turku Uni Central Hospital; Oncology Clinics
🇫🇮Turku, Finland
National Hospital Organization Osaka National Hospital; Breast Surgery
🇯🇵Osaka, Japan
University of Tennessee Cancer Institute;Hem-Onc Consultants
🇺🇸Knoxville, Tennessee, United States
Policlinico Ospedaliero Ss Annunziata; U.O. Di Clinica Oncologica
🇮🇹Chieti, Abruzzo, Italy
Ospedale Di Macerata; Oncologia
🇮🇹Macerata, Marche, Italy
Southern Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Shizuoka Cancer Center; Female Internal Medicine
🇯🇵Shizuoka, Japan
The Cancer Inst. Hosp. of JFCR; Breast Oncology Center
🇯🇵Tokyo, Japan
FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF
🇷🇺St Petersburg, Leningrad, Russian Federation
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Berkshire Hematology, Oncology Pc
🇺🇸Pittsfield, Massachusetts, United States
NEA Baptist Clinic
🇺🇸Jonesboro, Arkansas, United States
Kumamoto Shinto General Hospital; Breast Cancer Center
🇯🇵Kumamoto, Japan
SCRI Tennessee Oncology Chattanooga
🇺🇸Chattanooga, Tennessee, United States
HonorHealth Research Institute - Bisgrove
🇺🇸Scottsdale, Arizona, United States
St. Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
Oncology and Hematology Specialists
🇺🇸Mountain Lakes, New Jersey, United States
Hospital Solca Quito; Oncologia
🇪🇨Quito, Ecuador
Saitama Cancer Center, Breast Oncology
🇯🇵Saitama, Japan
Ausl Frosinone - Ospedale Umberto I; Divisione Di Oncologia
🇮🇹Frosinone, Lazio, Italy
Solca Guayaquil- Sociedad de Lucha Contra El Cáncer; Oncology
🇪🇨Guayaquil, Ecuador
Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii
🇵🇱Warszawa, Poland
Ivanovo Regional Oncology Dispensary
🇷🇺Ivanovo, Russian Federation
Cancer & Hematology Centers of Western Michigan
🇺🇸Grand Rapids, Michigan, United States
Cancer & Hematology Center of West Michigan
🇺🇸Grand Rapids, Michigan, United States
Cancer Center of Acadiana at Lafayette General
🇺🇸Lafayette, Louisiana, United States
Private Practice Robert R. Carroll, Md, Pa
🇺🇸Gainesville, Florida, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
Upstate Ny Cancer Research & Education Foundation
🇺🇸Rochester, New York, United States
Oncology Care Associates PLLC
🇺🇸Saint Joseph, Michigan, United States
Georgetown University Medical Center Lombardi Cancer Center
🇺🇸Washington, District of Columbia, United States
Pamela Youde Nethersole Eastern Hospital; Clinical Oncology
🇭🇰Hong Kong, Hong Kong