A Study of Palbociclib (PD-0332991) + Letrozole vs. Letrozole For 1st Line Treatment Of Postmenopausal Women With ER+/HER2- Advanced Breast Cancer (PALOMA-2)

Phase 3

Completed

• Conditions: Breast Neoplasms
• Interventions: Drug: Placebo; Drug: PD-0332991; Drug: Letrozole

• Registration Number: NCT01740427
• Lead Sponsor: Pfizer

Brief Summary

The study is designed to compare the clinical benefit following treatment with letrozole in combination with PD-0332991 versus letrozole in combination with placebo in postmenopausal women with ER(+)/HER2(-) advanced breast cancer who have not received prior systemic anti cancer therapies for their advanced/metastatic disease.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-11-26
• Study First Submitted QC: 2012-11-30
• Study First Posted: 2012-12-04
• Study Start: 2013-02-22
• Primary Completion: 2016-02-26
• Results First Submitted: 2016-10-21
• Results First Submitted QC: 2017-03-16
• Results First Posted: 2017-04-26
• Study Completion: 2023-11-09
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-22
• Last Update Posted: 2024-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 666

Inclusion Criteria

• Adult women with locoregionally recurrent or metastatic disease not amenable to curative therapy.
• Confirmed diagnosis of ER positive breast cancer
• No prior systemic anti-cancer therapy for advanced ER+ disease.
• Postmenopausal women
• Measurable disease as per Response Evaluation Criterion in Solid Tumors [RECIST] or bone-only disease
• Eastern Cooperative Oncology Group [ECOG] 0-2
• Adequate organ and marrow function
• Patient must agree to provide tumor tissue

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Exclusion Criteria

• Confirmed diagnosis of HER2 positive disease
• Patients with advanced, symptomatic, visceral spread that are at risk of life threatening complication in the short term
• Known uncontrolled or symptomatic CNS metastases
• Prior (neo)adjuvant treatment with letrozole or anastrozole with DFI ≤ 12-months from completion of treatment.
• Prior treatment with any CDK 4/6 inhibitor.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + Letrozole	Placebo	Placebo, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).
Placebo + Letrozole	Letrozole	Placebo, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).
PD-0332991 + Letrozole	Letrozole	PD-0332991, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).
PD-0332991 + Letrozole	PD-0332991	PD-0332991, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) as Assessed by the Investigator	From randomization date to date of first documentation of progression or death (up to approximately 2.5 years)	PFS is defined as the time from the date of randomization to the date of the first documentation of objective tumor progression as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or death due to any cause in the absence of documented PD, whichever occurs first. If tumor progression data include more than 1 date, the first date will be used. PFS (in months) will be calculated as (first event date - randomization date +1)/30.4. Progression is defined using RECIST v1.1, as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions, or the appearance of new lesions.

Secondary Outcome Measures

Name	Time	Method
Objective Response as Assessed by the Investigator	From randomization until end of treatment (up to approximately 2.5 years)	Objective Response (OR) defined as overall complete response (CR) or partial response (PR) according to RECIST v1.1. Objective Response Rate (ORR) is defined as proportion of participants with CR or PR relative to all randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment, or who died, progressed/ dropped out for any reason prior to reaching a CR or PR were counted as non-responders in assessment of ORR. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \<10mm). PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. Stable Disease: neither sufficient shrinkage nor increase to qualify for disease progression.
Objective Response: Participants With Measurable Disease at Baseline as Assessed by the Investigator	From randomization until end of treatment (up to approximately 2.5 years)	The OR is defined as the overall CR or PR according to the RECIST v1.1. ORR is defined as proportion of participants with CR or PR relative to all randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment, or who died, progressed/ dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the assessment of ORR. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \<10mm). PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. Stable Disease: neither sufficient shrinkage nor increase to qualify for disease progression.
Duration of Response (DR)	From randomization until end of treatment (up to approximately 2.5 years)	DR is defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurs first. If tumor progression data included more than 1 date, the first date will be used. DR was calculated as \[the date response ended (i.e. date of PD or death) - first CR or PR date + 1)\]/30.4. DR would only be calculated for the subgroup of participants with an objective tumor response. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \<10mm). PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions.The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. Stable Disease: neither sufficient shrinkage nor increase to qualify for disease progression.
Disease Control (DC)/Clinical Benefit Response (CBR)	From randomization until end of treatment (up to approximately 2.5 years)	DC is defined as overall CR, PR, or stable disease (SD) \>=24 weeks according to RECIST version 1.1. Disease Control Rate (DCR) is defined as participants with CR, PR, or SD \>=24 weeks relative to all randomized participants. Participants who do not have on-study radiographic tumor reevaluation, who received anti-tumor treatment, a best response of SD\>=24 weeks, or who died, progressed, or dropped out for any reason prior to achieving reaching a CR or PR and a best response of SD\>=24 weeks was counted as non-responders in DCR. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \<10mm). PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. SD: neither sufficient shrinkage nor increase to qualify for disease progression.
PFS by Tumor Tissue Biomarkers Status, Including Genes (eg, Copy Numbers of CCND1, CDKN2A), Proteins (eg, Ki67, pRb), and RNA Expression (eg, cdk4, cdk6)	From randomization until end of treatment (up to approximately 24 Months)	PFS by biomarker status by Investigator assessment. Progression is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Positive is defined as H-Score \>=1 and negative as H-Score \<1. H-Score is calculated as the sum of the % of cells at each level of staining intensity (0, 1+, 2+, and 3+) multiplied by the staining intensity value: H-Score = (% at 0)\*0 + (% at 1+)\*1 + (% at 2+)\*2 + (% at 3+)\*3. H-Score values range from 0 to 300. ER stands for estrogen receptor and Rb stands for retinoblastoma susceptibility gene product.
Corrected QT Interval (QTc) Time-Matched Change From Baseline on Cycle 1 Day 14	Time-matched triplicate ECGs were collected at 0 (predose), 2, 4, 6 and 8 hours on Day 0 and on Cycle1 Day14	Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and sent to a central laboratory for blinded manual adjudication. The average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR), by Bazette's formula (QTcB = QT divided by square root of RR) and corrected QT interval according to study-specific criteria (QTcS). Time-matched change from baseline values were reported for QTc analysis population.
Percentage of Participants With Corrected QT Interval (QTc)	For safety monitoring triplicate ECGs were obtained at 0 hour (pre-dose) on Day 1 of Cycle 1, Day 14 of Cycles 1 and Cycle 2, then on Day 1 of Cycles 4, 7, and 10 (ECGs beyond Cycle 10 were performed as clinically indicated)	Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and sent to a central laboratory for blinded manual adjudication. The average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR), by Bazette's formula (QTcB = QT divided by square root of RR) and corrected QT interval according to study-specific criteria (QTcS). Percentage of participants with post-baseline maximum absolute values and maximum increase from baseline were summarized for the safety analysis population.
Observed Plasma Trough Concentration (Ctrough) at Steady-State	0 hour (predose) on Day 14 of cycles 1 and 2	Summary of plasma palbociclib within-participant mean steady-state trough concentrations.
Change From Baseline Between Treatment Comparison in Euro Quality of Life (EQ-5D) Index	From Baseline up to 2.5 years	The EuroQol EQ-5D is a 6-item instrument designed to assess health status in terms of a single index value or utility score. It contains 5 descriptors of current health state (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) with each dimension having 3 levels of function (1=no problem, 2=some problem, and 3=extreme problem). The scores on the 5 descriptors are summarized to create a single summary score. An overall utility score is calculated based on these domains, with a range score from 0 (worse health scenario) to a maximum of 1.0 (best health scenario).
Change From Baseline Between Treatment Comparison in Functional Assessment of Cancer Therapy-Breast (FACT-B)	From Baseline up to 2.5 years	FACT is a modular approach to assess participant health-related quality of life using a 'core' set of questions (FACT-G) as well as a cancer site-specific module. The FACT-G is a 27-item compilation of general questions divided into 4 domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. The FACT-B consisted of the FACT-G (27-item) and a breast-specific module: a 10-item instrument designed to assess participant concerns relating to breast cancer. For all questions, participants were asked to respond to a five-level scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much. FACT-B total score = Physical Well-Being + Social/Family Well-Being + Emotional Well-Being + Functional Well-Being + Breast Cancer Subscale. As each of the items ranges from 0-4, the range of possible scores is 0-144, with 0 being the worst possible score and 144 the best.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs): All Causalities	From date of randomization up to 28 days after last dose of study drug (final analysis till study completion, approximately up to 10.51 years)	An AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. SAE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization; resulted in persistent or significant disability or in congenital anomaly/birth defect. TEAE were events that occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Severity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0 as Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening and Grade 5 = death related to AE. Discontinuation included permanent, temporary discontinuation and dose reduction due to AEs.
Overall Survival (OS): Primary Analysis	From date of randomization until death due to any cause or censored, (assessed up to data cut-off date of 15-Nov-2021, approximately 8.7 years)	OS was defined as the time from date of randomization to date of death due to any cause. Participants without survival data beyond the date of their last follow-up were censored on the last date they were known to be alive. Data for this outcome measure was reported at primary analysis.
Overall Survival (OS): Final Analysis	From date of randomization until death due to any cause or censored (final analysis till study completion, approximately up to 10.51 years)	OS was defined as the time from date of randomization to date of death due to any cause. Participants without survival data beyond the date of their last follow-up were censored on the last date they were known to be alive. Data for this outcome measure was reported at final analysis.
Survival Probability at 1 Year, 2 Year and 3 Year	1, 2 and 3 years after randomization	One, two or three-year survival probability was defined as the probability of survival 1 year, 2 or 3 years after the date of randomization. The survival probability was estimated using the Kaplan-Meier method and 2-sided 95% confidence interval (CI) was calculated using the product limit method.
Number of Participants With Laboratory Abnormalities by Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade	From randomization up to 28 days after last dose of study drug (assessed up to analysis date of 15-Nov-2021, approximately 8.7 years)	Laboratory abnormalities included anemia, hemoglobin increased, neutrophils (absolute), platelets, white blood cells, alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), bilirubin (total), creatinine, hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypokalemia, hypomagnesemia and hyponatremia. Laboratory abnormalities were graded by CTCAE version (v) 4.0 as Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = life-threatening. Categories with at least 1 non-zero data values are reported.

Trial Locations

Locations (273)

Translational Research Management; 🇺🇸 Los Angeles, California, United States

UCLA West Medical Pharmacy: Drug Management Only; 🇺🇸 Los Angeles, California, United States

UCLA West Medical Pharmacy; 🇺🇸 Los Angeles, California, United States

Drug Management Only: UCLA West Medical Pharmacy, Attn: Steven L Wong, Pharm.D.; 🇺🇸 Los Angeles, California, United States

UCLA West Medical Pharmacy, Attn: Steven L. Wong; 🇺🇸 Los Angeles, California, United States

UCLA Hematology/ Oncology- Irvine; 🇺🇸 Irvine, California, United States

UCLA Hematology Oncology- Laguna Hills; 🇺🇸 Laguna Hills, California, United States

UCLA West Medical Pharmacy; Drug Management Only; 🇺🇸 Los Angeles, California, United States

Administrative Address: UCLA Hematology/Oncology; 🇺🇸 Los Angeles, California, United States

Regulatory Management Only: TRIO-US Central Administration; 🇺🇸 Los Angeles, California, United States

Ronald Reagan UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

TRIO-US Central Administration: Regulatory Management Only; 🇺🇸 Los Angeles, California, United States

TRIO-US Central Administration; 🇺🇸 Los Angeles, California, United States

UCLA Hematology Oncology; 🇺🇸 Los Angeles, California, United States

UCLA Hematology/Oncology; 🇺🇸 Los Angeles, California, United States

Memorial Cancer Institute at Memorial Regional Hospital; 🇺🇸 Hollywood, Florida, United States

Memorial Breast Cancer Center at Memorial Hospital West; 🇺🇸 Pembroke Pines, Florida, United States

Sylvester Comprehensive Cancer Center Plantation; 🇺🇸 Plantation, Florida, United States

Grady Health System; 🇺🇸 Atlanta, Georgia, United States

Emory University Hospital Midtown; 🇺🇸 Atlanta, Georgia, United States

Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Northwest Georgia Oncology Centers, PC; 🇺🇸 Marietta, Georgia, United States

The Mark M. Connolly Center for Cancer and Specialty Care; 🇺🇸 Chicago, Illinois, United States

Presence Infusion Care- Skokie; 🇺🇸 Skokie, Illinois, United States

Texas Oncology-Baylor Charles A. Sammons Cancer Center; 🇺🇸 Dallas, Texas, United States

WVU Medicine; 🇺🇸 Morgantown, West Virginia, United States

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

The University of Texas MD Anderson Cancer Center, Department of Breast Medical Oncology; 🇺🇸 Houston, Texas, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Calvary Mater Newcastle; 🇦🇺 Waratah, New South Wales, Australia

Torrance Health Association, DBa Torrance Memorial Physician Network; 🇺🇸 Redondo Beach, California, United States

San Luis Obispo Oncology and Hematology Health Center/ Pacific Central Coast Health Centers; 🇺🇸 San Luis Obispo, California, United States

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States

UZ Brussel; 🇧🇪 Brussel, Belgium

Hopital du Sacre-Coeur; 🇨🇦 Montreal, Quebec, Canada

Institut de Cancerologie de l'Ouest- Paul Papin; 🇫🇷 Anger Cedex 02, France

Centre François Baclesse; 🇫🇷 Caen Cedex 5, France

Fakultni nemocnice Hradec Kralove, Klinika onkologie a radiologie; 🇨🇿 Hradec Kralove, Czechia

Institut Curie, Departement d'Oncologie Medicale; 🇫🇷 Paris Cedex 05, France

Orszagos Onkologiai Intezet ,; 🇭🇺 Budapest, Hungary

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont, Altalanos Orvostudomanyi Kar; 🇭🇺 Szeged, Hungary

St Vincents University Hospital; 🇮🇪 Dublin 4, Ireland

National Hospital Organization Hokkaido Cancer Center; 🇯🇵 Sapporo, Hokkaido, Japan

Niepubliczny Zakład Opieki Zdrowotnej "Onko-Dent" SP.P. G.L. Słomian; 🇵🇱 Zory, Poland

Regional Budgetary Healthcare Institution Kursk Regional Clinical; 🇷🇺 Kursk, Kursk Region, Russian Federation

Complejo Hospitalario de Jaen; 🇪🇸 Jaen, Spain

Instituto Catalan de Oncologia L'Hospitalet; 🇪🇸 L'Hospitalet De Llobregat (Barcelona), Spain

Hospital Universitario Arnau de Vilanova de Lleida; 🇪🇸 Lleida, Spain

Mackay Memory Hospital; 🇨🇳 Taipei, Taiwan

State institution "Zaporizhzhia Medical Academy of Postgraduate Education MOH Ukraine",; 🇺🇦 Zaporizhzhya, Ukraine

Southern California Permanente Medical Group; 🇺🇸 San Diego, California, United States

Regulatory Office: Comprehensive Cancer Centers of Nevada Research Department; 🇺🇸 Las Vegas, Nevada, United States

Istituti Fisioterapici Ospitalieri; 🇮🇹 Roma, Italy

Ospedale SS Trinita; 🇮🇹 Sora (FR), Italy

Kent Oncology Center; 🇬🇧 Maidstone, Kent, United Kingdom

Fiona Stanley Hospital; 🇦🇺 Murdoch, Western Australia, Australia

Hospital Universitario de Canarias; 🇪🇸 La Laguna, Santa CRUZ DE Tenerife, Spain

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

University of California San Francisco - Helen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States

Northwest Cancer Specialists, PC; 🇺🇸 Portland, Oregon, United States

Kaiser Permanente Northwest Region; 🇺🇸 Portland, Oregon, United States

OHSU Center for Health and Healing 2; 🇺🇸 Portland, Oregon, United States

OHSU Research Pharmacy Services; 🇺🇸 Portland, Oregon, United States

Institut Jules Bordet; 🇧🇪 Brussels, Belgium

Grand Hopital de Charleroi / Service d'Hematologie et Oncologie; 🇧🇪 Charleroi, Belgium

CHU Start Tilman; 🇧🇪 Liege, Belgium

MedStar Georgetown University Hospital; 🇺🇸 Washington, District of Columbia, United States

Oncologie; 🇧🇪 Brussels, Belgium

Diagnoscan Magyarorszag Kft.; 🇭🇺 Szeged, Hungary

Hiroshima City Hiroshima Citizens Hospital; 🇯🇵 Hiroshima, Japan

Iwate Medical University Hospital; 🇯🇵 Iwate, Japan

The West Clinic, PC dba West Cancer Centre; 🇺🇸 Memphis, Tennessee, United States

Epworth Healthcare; 🇦🇺 Richmond, Victoria, Australia

McGill University Health Centre (MUHC), Glen Site, Cedars Cancer Centre; 🇨🇦 Montreal, Quebec, Canada

Maroondah Hospital; 🇦🇺 Ringwood East, Victoria, Australia

Beatson Institute for Cancer Research; 🇬🇧 Glasgow, Scotland, United Kingdom

Tennessee Oncology PLLC; 🇺🇸 Smyrna, Tennessee, United States

Országos Onkológiai Intézet "B" Belgyogyaszati osztaly; 🇭🇺 Budapest, Hungary

National Cancer Center Hospital East; 🇯🇵 Kashiwa, Chiba, Japan

Saitama Cancer Center; 🇯🇵 Kita-adachi-gun, Saitama, Japan

Republican Clinical Hospital n.a. G.G. Kuvatov; 🇷🇺 Ufa, Russian Federation

Municipal Non-profit Enterprise "Regional Centre of Oncology"; 🇺🇦 Kharkiv, Ukraine

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

Tennessee Oncology, PLLC; 🇺🇸 Shelbyville, Tennessee, United States

Royal Melbourne Hospital; 🇦🇺 Parkville, Victoria, Australia

Petz Aladar Megyei Oktato Korhaz, Onkoradiologiai Osztaly; 🇭🇺 Györ, Hungary

Szent Margit Korhaz; 🇭🇺 Budapest, Hungary

CHR East Belgium - Verviers; 🇧🇪 Verviers, Belgium

Mater Misericordiae University Hospital; 🇮🇪 Dublin, Ireland

BC Cancer Agency-Fraser Valley Centre; 🇨🇦 Surrey, British Columbia, Canada

Országos Onkológiai Intézet, Nuklearis Medicina Osztaly; 🇭🇺 Budapest, Hungary

Center Hospitalier Affilie Universitaire de Quebec, Universite Laval, Hopital du Saint Sacrement; 🇨🇦 Quebec City, Quebec, Canada

Országos Onkológiai Intézet, Radiologiai Diagnosztikai Osztily; 🇭🇺 Budapest, Hungary

Szegedi Tudomanyegyetem Altalanos Orvosi Kar, Patologia Intezet; 🇭🇺 Szeged, Hungary

Kumamoto City Hospital; 🇯🇵 Kumamoto-shi, Kumamoto, Japan

Chiba Cancer Center; 🇯🇵 Chiba, Japan

Niigata Cancer Center Hospital 2-15-3; 🇯🇵 Niigata, Japan

GUZ Republic Clinical Oncology Dispensary of Ministry of Health of Republic of Tatarstan; 🇷🇺 Kazan, Russian Federation

Non-State Health Care agency "Road Clinical Hospital of PLC" Russian Railways; 🇷🇺 St Petersburg, Russian Federation

National Taiwan University Hospital; 🇨🇳 Taipei City, Taiwan

National Hospital Organization Shikoku Cancer Center; 🇯🇵 Matsuyama-city, Ehime, Japan

National Hospital Organization Osaka National Hospital; 🇯🇵 Osaka, Japan

Europejskie Centrum Zdrowia Otwock; 🇵🇱 Otwock, Mazovia, Poland

National Cancer Center Hospital; 🇯🇵 Chuo-Ku, Tokyo, Japan

State Budget Healthcate Institution "Leningrad Region Oncology Dispensary"; 🇷🇺 Kuzmolovo, Leningrad Region, Russian Federation

Lviv State Oncologic Regional Treatment and Diagnostic Center, Chemotherapy Department; 🇺🇦 Lviv, Ukraine

Federal State Budget Institution; 🇷🇺 Moscow, Russian Federation

Hospital Universitari Son Espases; 🇪🇸 Palma de Mallorca, Islas Baleares, Spain

State Institution Dnipropetrovsk Medical Academy at the Ministry of Health of Ukraine; 🇺🇦 Dnipro, Ukraine

MI "Dnipropetrovsk City Multidisciplinary Clinical Hospital No.4" of the Dnipropetrovsk City Council; 🇺🇦 Dnipro, Ukraine

Regional Municipal Establishment "Sumy Regional Clinical Oncology Dispensary", Thoracic Department; 🇺🇦 Sumy, Ukraine

City Oncology Centre of Central Municipal Clinical Hospital; 🇺🇦 Uzhgorod, Ukraine

MI "Zaporizhzhia Regional Clinical Oncology Dispensary" Zaporizhzhia Regional Assembly,; 🇺🇦 Zaporizhzhia, Ukraine

Municipal Medical Institution "Makiivka City Hospital No.2 of Donetsk Region"; 🇺🇦 Makiivka, Ukraine

Walter Reed National Military Medical Center; 🇺🇸 Bethesda, Maryland, United States

University of Michigan Health System; 🇺🇸 Ann Arbor, Michigan, United States

Los Angeles Hematology/Oncology Medical Group; 🇺🇸 Los Angeles, California, United States

St. Joseph Heritage Healthcare; 🇺🇸 Fullerton, California, United States

Beverly Hills Cancer Center; 🇺🇸 Beverly Hills, California, United States

Drug Management Only: TRIO-US Pharmacy UCLA Medical Plaza, Attn: Steven L Wong, Pharm.D.; 🇺🇸 Los Angeles, California, United States

UCLA Hematology/ Oncology- Pasadena; 🇺🇸 Pasadena, California, United States

Central Coast Medical Oncology Corporation; 🇺🇸 Santa Maria, California, United States

UCLA Santa Monica Medical Center and Orthopaedic Hospital; 🇺🇸 Santa Monica, California, United States

Stanford Women's Cancer Center; 🇺🇸 Stanford, California, United States

Wellness Oncology & Hematology; 🇺🇸 West Hills, California, United States

UCLA Hematology/Oncology- Westlake; 🇺🇸 Westlake Village, California, United States

St. Mary's Hospital Regional Cancer Center; 🇺🇸 Grand Junction, Colorado, United States

Whittingham Cancer Center @ Norwalk Hospital; 🇺🇸 Norwalk, Connecticut, United States

Sylvester at Deerfield Beach; 🇺🇸 Deerfield Beach, Florida, United States

Memorial Breast Cancer Center at Memorial Regional Hospital; 🇺🇸 Hollywood, Florida, United States

Cancer Specialists of North Florida-Southpoint; 🇺🇸 Jacksonville, Florida, United States

Memorial Cancer Institute at Memorial Hospital West; 🇺🇸 Pembroke Pines, Florida, United States

Memorial Hospital West; 🇺🇸 Pembroke Pines, Florida, United States

Memorial Regional Hospital; 🇺🇸 Hollywood, Florida, United States

Cancer Specialist of North Florida, Pharmacy; 🇺🇸 Jacksonville, Florida, United States

Cancer Specialists of North Florida - St. Augustine; 🇺🇸 Saint Augustine, Florida, United States

The Emory Clinic; 🇺🇸 Atlanta, Georgia, United States

Kootenai Clinic Cancer Services; 🇺🇸 Post Falls, Idaho, United States

Carle Foundation Hospital DBA Carle Cancer Center; 🇺🇸 Urbana, Illinois, United States

Presence Infusion Care- Evanston; 🇺🇸 Evanston, Illinois, United States

University of Maryland, Greenebaum Cancer Center; 🇺🇸 Baltimore, Maryland, United States

The West Clinic, PC; 🇺🇸 Corinth, Mississippi, United States

Mercy Clinic St. Louis Cancer and Breast Institute; 🇺🇸 Saint Louis, Missouri, United States

Park Nicollet Frauenshuh Cancer Center; 🇺🇸 Saint Louis Park, Minnesota, United States

Mercy Hospital St. Louis; 🇺🇸 Saint Louis, Missouri, United States

Mercy Hospital St. Louis - David C. Pratt Cancer Center; 🇺🇸 Saint Louis, Missouri, United States

Saint Francis Medical Center; 🇺🇸 Hastings, Nebraska, United States

Saint Francis Medical Center, Saint Francis Cancer Treatment Center; 🇺🇸 Grand Island, Nebraska, United States

Comprehensive Cancer Centers of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Stony Brook University- Cancer Center; 🇺🇸 Stony Brook, New York, United States

CareMount Medical; 🇺🇸 Mount Kisco, New York, United States

Northern Westchester Hospital; 🇺🇸 Mount Kisco, New York, United States

Northwest Cancer Specialists, P.C.; 🇺🇸 Vancouver, Washington, United States

OHSU Center for Health and Healing; 🇺🇸 Portland, Oregon, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Texas Oncology-west Texas; 🇺🇸 El Paso, Texas, United States

Texas oncology-West Texas; 🇺🇸 El Paso, Texas, United States

Texas Oncology-Dallas Presbyterian Hospital; 🇺🇸 Dallas, Texas, United States

Texas oncology-west Texas; 🇺🇸 El Paso, Texas, United States

Investigational Products Center (IPC); 🇺🇸 Fort Worth, Texas, United States

Oncology & Hematology Associates of Southwest Virginia, Inc. D.B.A Blue Ridge Cancer Care; 🇺🇸 Salem, Virginia, United States

Oncology & Hematology Associates of Southwest Virginia, INC., D.B.A. Blue Rigde Cancer Care; 🇺🇸 Wytheville, Virginia, United States

The University of Texas MD Anderson Cancer Center.; 🇺🇸 Houston, Texas, United States

Shenandoah Oncology PC; 🇺🇸 Winchester, Virginia, United States

US Oncology Investigational Products Center; 🇺🇸 Irving, Texas, United States

Virginia oncology Associates; 🇺🇸 Norfolk, Virginia, United States

Virginia Oncology Associates; 🇺🇸 Virginia Beach, Virginia, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Northwest Cancer Specialists P.C.; 🇺🇸 Vancouver, Washington, United States

University of Wisconsin; 🇺🇸 Madison, Wisconsin, United States

Laverty Pathology; 🇦🇺 Port Macquarie, New South Wales, Australia

Mid North Coast Diagnostic Imaging; 🇦🇺 Port Macquarie, New South Wales, Australia

Icon Cancer Care; 🇦🇺 Auchenflower, Queensland, Australia

Icon Cancer Care Corporate Office; 🇦🇺 South Brisbane, Queensland, Australia

Sunshine Coast University Hospital; 🇦🇺 Birtinya, Queensland, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

Bendigo Health Care Group, The Bendigo Hospital Campus; 🇦🇺 Bendigo, Victoria, Australia

Goulburn Valley Health; 🇦🇺 Shepparton, Victoria, Australia

Northern Hospital; 🇦🇺 Epping, Victoria, Australia

Gasthuis Zusters Antwerpen - Campus Sint- Augustinus; 🇧🇪 Wilrijk, Antwerpen, Belgium

Tom Baker Cancer Centre; 🇨🇦 Calgary, Alberta, Canada

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg; 🇧🇪 Leuven, Belgium

Cross Cancer Institute; 🇨🇦 Edmonton, Alberta, Canada

British Columbia Cancer Agency-Vancouver Centre; 🇨🇦 Vancouver, British Columbia, Canada

Southlake Regional Health Centre- Stronach Regional Cancer Centre; 🇨🇦 Newmarket, Ontario, Canada

London Regional Cancer Program; 🇨🇦 London, Ontario, Canada

QEII Health Sciences Centre, Victoria General Site; 🇨🇦 Halifax, Nova Scotia, Canada

Sunnybrook Research Institute; 🇨🇦 Toronto, Ontario, Canada

St. Michaels Hospital; 🇨🇦 Toronto, Ontario, Canada

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Allan Blair Cancer Centre; 🇨🇦 Regina, Saskatchewan, Canada

Centre Georges François Leclerc; 🇫🇷 Dijon, France

Centre Eugene Marquis; 🇫🇷 Rennes, France

CHD Vendée; 🇫🇷 La Roche Sur Yon, France

Centre Val d'Aurelle,; 🇫🇷 Montpellier CEDEX 5, France

Centre Antoine Lacassagne; 🇫🇷 Nice cedex 2, France

Institut de Cancérologie de l'Ouest-Rene Gauducheau; 🇫🇷 St Herblain, France

Hopital Rene Huguenin/Institut Curie; 🇫🇷 Saint-Cloud, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

Institut Claudius Regaud- Cancer Comprehensive Center- IUCT-O-Medical Oncology Department; 🇫🇷 Toulouse CEDEX-9, France

IOZ- Munchen, PGM- Studien GmbH; 🇩🇪 Muenchen, Bavaria, Germany

Universitatsklinikum Erlangen, Frauenklinik; 🇩🇪 Erlangen, Germany

Klinikverbund Sudwest - Kliniken Sidelfingen-Boblingen; 🇩🇪 Boblingen, Germany

University Hospital Carl Gustav Carus - Department for Obstetrics and Gynecology.; 🇩🇪 Dresden, Germany

Universitaetsklinikum Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Universitatsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Gynakologie und Geburtshilfe; 🇩🇪 Kiel, Germany

Universitaetsklinikum Magdeburg AOR Universitaetsfrauenklinik; 🇩🇪 Magdeburg, Germany

Frauenklinik und Poliklinik Klinikum rechts der Isar, Technische Universitaet Muenchen; 🇩🇪 Muenchen, Germany

Katholisches Klinikum Mainz; 🇩🇪 Mainz, Germany

Rotkreuzklinikum Munchen, Frauenklinik,; 🇩🇪 Munich, Germany

Klinikum Mutterhaus; 🇩🇪 Trier, Germany

Breast Cancer, University of Munich, Grosshadern Hospital; 🇩🇪 Munich, Germany

Affidea Diagnosztika Kft.; 🇭🇺 Budapest, Hungary

Josa Andras Teaching Hospital,; 🇭🇺 Nyiregyhaza, Hungary

St. James Hospital; 🇮🇪 Dublin, Ireland

Bon Secours Hospital; 🇮🇪 Cork, Ireland

Beaumont Hospital; 🇮🇪 Dublin, Ireland

Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi; 🇮🇹 Bologna, BO, Italy

Department of Medical Oncology; 🇮🇪 Galway, Ireland

Mid Western Regional Hospital; 🇮🇪 Limerick, Ireland

Waterford Regional Hospital; 🇮🇪 Waterford, Ireland

Azienda Ospedaliera San Giuseppe Moscati; 🇮🇹 Avellino, Italy

Azienda Ospedaliero-Universitaria Pisana; 🇮🇹 Pisa, Italy

Irccs Irst; 🇮🇹 Meldola, FC, Italy

IRCCS - Istituto Europeo di Oncologia; 🇮🇹 Milano, Milan, Italy

Aichi Cancer Center Hospital; 🇯🇵 Nagoya, Aichi, Japan

National Hospital Organization Kyushu Cancer Center; 🇯🇵 Fukuoka, Japan

Kumamoto University Hospital; 🇯🇵 Kumamoto, Japan

Hakuaikai Medical Corporation Sagara Hospital; 🇯🇵 Kagoshima, Japan

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Gyeonggi-do, Korea, Republic of

Severance Hospital, Yonsei University Health System; 🇰🇷 Seodaemun-gu, Seoul, Korea, Republic of

National Cancer Center, Center for Breast Cancer; 🇰🇷 Goyang-si, Gyeonggi-do, Korea, Republic of

Oncology and Radiotherapy Clinic; 🇵🇱 Gdańsk, Poland

State Budget Healthcare Institution Moscow City Oncology Hospital; 🇷🇺 Moscow Area, Russian Federation

Budget Institution of Healthcare; 🇷🇺 Omsk, Russian Federation

Ryazan Regional Clinical Oncology Dispensary; 🇷🇺 Ryazan, Russian Federation

Saint-Petersburg State Budget Healthcare Institution (SBHCI); 🇷🇺 Saint-Petersburg, Russian Federation

Consorci Sanitari de Terrassa; 🇪🇸 Terrassa, Barcelona, Spain

Hospital Universitari Germans Trias i Pujol; 🇪🇸 Badalona, Barcelona, Spain

State Budget Medical Institution Republican Clinical Oncology; 🇷🇺 Ufa, Russian Federation

SBHI of Republic of Bashkortostan Emergency Hospital; 🇷🇺 Ufa, Russian Federation

Hospital Universitario Fundacion de Alcorcon; 🇪🇸 Alcorcon, Madrid, Spain

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

Hospital Universitario Infanta Cristina; 🇪🇸 Badajoz, Spain

Hospital de Donostia; 🇪🇸 Donostia- San Sebastian, Spain

Hospital Clinic I Provincial; 🇪🇸 Barcelona, Spain

Centro Oncologico de Galicia; 🇪🇸 La Coruna, Spain

HOSPITAL Universitario 12 DE OCTUBRE; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen Macarena; 🇪🇸 Sevilla, Spain

Centro Oncologico MD Anderson Internacional España; 🇪🇸 Madrid, Spain

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Spain

Instituto Valenciano de Oncologia; 🇪🇸 Valencia, Spain

Veterans General Hospital-Taipei; 🇨🇳 Taipei City, Taiwan

Institute of Postgraduate education and preuniversity preparing of Uzhgorod National Univ.; 🇺🇦 Uzhgorod, Ukraine

Edinburgh Cancer Centre, Western General Hospital; 🇬🇧 Edinburgh, Scotland, United Kingdom

Guys Hospital; 🇬🇧 London, United Kingdom

The Royal Marsden NHS Foundation Trust; 🇬🇧 London, United Kingdom

Christie Hospital NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

The Research And Development Office, The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

Hospital General Universitario Gregorio Marañon; 🇪🇸 Madrid, Spain

Hospital Madrid Universitario Sanchinarro; 🇪🇸 Madrid, Spain

Seoul National University Hospital / Department of Internal Medicine; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center, Division of Oncology, Department of Internal Medicine; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center, Division of Hematology-Oncology, Department of Medicine; 🇰🇷 Seoul, Korea, Republic of

Smilow Cancer Hospital at Yale New Haven; 🇺🇸 New Haven, Connecticut, United States

Orlando Health, Inc.; 🇺🇸 Orlando, Florida, United States

James Graham Brown Cancer Center and University Hospital; 🇺🇸 Louisville, Kentucky, United States

James Graham Brown Cancer Center; 🇺🇸 Louisville, Kentucky, United States

St Vincent's Hospital Sydney; 🇦🇺 Darlinghurst, New South Wales, Australia

Charing Cross Hospital; 🇬🇧 London, United Kingdom