A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer

Phase 3

Completed

• Conditions: Triple Negative Breast Neoplasms
• Interventions: Drug: Placebo; Drug: Atezolizumab; Drug: Gemcitabine; Drug: Capecitabine; Drug: Carboplatin

• Registration Number: NCT03371017
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This study will evaluate the efficacy and safety of atezolizumab plus chemotherapy compared with placebo plus chemotherapy in patients with inoperable recurrent triple-negative breast cancer (TNBC).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-11-21
• Study First Submitted QC: 2017-12-07
• Study First Posted: 2017-12-13
• Study Start: 2018-01-11
• Primary Completion: 2024-10-23
• Study Completion: 2024-10-23
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-07
• Last Update Posted: 2024-11-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 595

Inclusion Criteria

• Histologically confirmed triple negative breast cancer (TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic
• Documented disease progression occurring within 12 months from the last treatment with curative intent
• Prior treatment (of early breast cancer) with an anthracycline and taxane
• Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence. Prior radiation therapy for recurrent disease is permitted
• Measurable or non-measurable disease, as defined by RECIST 1.1
• Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumour block (preferred) or at least 17 unstained slides obtained from relapsed metastatic or locally advanced diseases may be submitted, if clinically feasible, with an associated pathology report, if available. If a fresh tumour sample is not clinically feasible, either the diagnosis sample, the primary surgical resection sample, or the most recent FFPE tumour biopsy sample should be used.
• Eastern Cooperative Oncology Group performance status 0-1
• Life expectancy ≥ 12 weeks
• Adequate haematologic and end-organ function
• Negative human immunodeficiency virus (HIV) test ---Negative hepatitis B surface antigen (HBsAg) test at screening
• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
• The HBV DNA test will be performed only for patients who have a negative HBsAg and a positive HBcAb test.
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening.
• Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of ≤1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of capecitabine, whichever is later. In addition, women must refrain from donating eggs during the same time period.
• Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm

Inclusion criteria for patients enrolled after the recruitment of all-comers is complete:

-PD-L1-positive tumour status (assessed centrally prior to randomisation), defined as PD-L1 expression on tumour-infiltrating immune cells (IC) of 1% or greater.

Exclusion Criteria

• Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomisation
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
• Symptomatic or rapid visceral progression
• No prior treatment with an anthracycline and taxane
• History of leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) (patients with indwelling catheters such as PleurX® are allowed)
• Uncontrolled tumour-related pain
• Uncontrolled or symptomatic hypercalcemia
• Malignancies other than TNBC within 5 years prior to randomisation)
• Significant cardiovascular disease, within 3 months prior to randomisation, unstable arrhythmias, or unstable angina
• Presence of an abnormal ECG
• Severe infection requiring oral or IV antibiotics within 4 weeks prior to randomisation, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
• Current treatment with anti-viral therapy for HBV.
• Major surgical procedure within 4 weeks prior to randomisation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis
• Treatment with investigational therapy within 28 days prior to randomisation
• Pregnant or lactating, or intending to become pregnant during or within 5 months after the last dose of atezolizumab, or within 6 months after the last dose of capecitabine, whichever is later.

Exclusion Criteria Related to Atezolizumab:

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation
• History of autoimmune disease
• Prior allogeneic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computerised tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Active tuberculosis
• Receipt of a live, attenuated vaccine within 4 weeks prior to randomisation or anticipation that a live, attenuated vaccine will be required during atezolizumab/placebo treatment or within 5 months after the last dose of atezolizumab/placebo
• Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents
• Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to randomisation
• Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to start of study treatment, or anticipated requirement for systemic immunosuppressive medications during the trial

Exclusion Criteria Related to Capecitabine:

• Inability to swallow pills
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis
• Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and unexpected reactions to fluoropyrimidine therapy in patients selected to receive capecitabine

Exclusion Criteria Related to Carboplatin/Gemcitabine:

-Hypersensitivity to platinum containing compounds or any component of carboplatin or gemcitabine drug formulations in patients selected to receive carboplatin and Gemcitabine

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Atezolizumab	Carboplatin	Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle
Placebo	Placebo	Participants will receive Placebo on day 1 of each 3-week treatment cycle
Atezolizumab	Atezolizumab	Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle
Atezolizumab	Capecitabine	Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle
Atezolizumab	Gemcitabine	Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle
Placebo	Gemcitabine	Participants will receive Placebo on day 1 of each 3-week treatment cycle
Placebo	Capecitabine	Participants will receive Placebo on day 1 of each 3-week treatment cycle
Placebo	Carboplatin	Participants will receive Placebo on day 1 of each 3-week treatment cycle

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS) in Modified Intent-To-Treat (mITT) Popluation	Baseline to end of study (approximately 58 months)	OS will be tested hierarchically in the following fixed order: * In the population with programmed deathligand 1 (PD-L1)-positive tumour status; * In the modified intent-to-treat (mITT) population
Overall Survival (OS) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	Baseline to end of study (approximately 58 months)	OS will be tested hierarchically in the following fixed order: * In the population with programmed deathligand 1 (PD-L1)-positive tumour status; * In the modified intent-to-treat (mITT) population

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)	PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first.; PFS will be tested hierarchically in the following fixed order: * In the PD-L1-positive population; * In the mITT population
Progression-Free Survival (PFS) in mITT population	Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)	PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first.; PFS will be tested hierarchically in the following fixed order: * In the PD-L1-positive population; * In the mITT population
Clinical Benefit Rate (CBR)	8 weeks for the first 12 months after treatment initiation and every 12 weeks thereafter until disease progression (through the end of study, approximately 58 months)	CBR is defined as the proportion of participants with a CR or a PR or stable disease as determined by the investigator according to RECIST 1.1.
Proportion of Participants Alive 12 Months	Randomization to 12 months post randomization
Clinical Benefit Rate (CBR) in China Population	8 weeks for the first 12 months after treatment initiation and every 12 weeks thereafter until disease progression (through the end of study, approximately 58 months)	CBR is defined as the proportion of participants with a CR or a PR or stable disease as determined by the investigator according to RECIST 1.1.
Time to Confirmed Deterioration (TTD) of GHS/QoL in China Population	Baseline to end of study (approximately 58 months)	TTD of GHS/QoL, defined by a minimally important decrease of ≥10 points at two consecutive assessment time-points on the GHS/QoL scale (Items 29, 30) of the EORTC QLQ-C30.
Proportion of Participants Alive 18 Months	Randomization to 18 months post randomization
ORR in Modified Intent-To-Treat (mITT) China Popluation	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)	ORR defined as the proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1. ORR will be tested hierarchically in the following fixed order: * In the PD-L1-positive population; * In the mITT population
Objective Response Rate (ORR) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)	ORR defined as the proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1. ORR will be tested hierarchically in the following fixed order: * In the PD-L1-positive population; * In the mITT population
Duration of Objective Response (DoR)	Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)	DoR as determined by the investigator according to RECIST 1.1.
Time to Confirmed Deterioration (TTD) of GHS/QoL	Baseline to end of study (approximately 58 months)	TTD of GHS/QoL, defined by a minimally important decrease of ≥10 points at two consecutive assessment time-points on the GHS/QoL scale (Items 29, 30) of the EORTC QLQ-C30.
Overall Survival (OS) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	Baseline to end of study (approximately 58 months)	OS will be tested hierarchically in the following fixed order: * In the population with programmed deathligand 1 (PD-L1)-positive tumour status; * In the modified intent-to-treat (mITT) population
Objective Response Rate (ORR) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)	ORR defined as the proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1. ORR will be tested hierarchically in the following fixed order: * In the PD-L1-positive population; * In the mITT population
Objective Response Rate (ORR) in Modified Intent-To-Treat (mITT) Popluation	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)	ORR defined as the proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1. ORR will be tested hierarchically in the following fixed order: * In the PD-L1-positive population; * In the mITT population
Confirmed Objective Response Rate (C-ORR)	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
Duration of Response for Confirmed Responders (C-DoR)	Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)
Relationship Between PD-L1 Protein Expression in Screening Tumour Tissue and Clinical Outcomes	Baseline to end of study (approximately 58 months)
Progression Free Survival (PFS) in mITT China Population	Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)	PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first.; PFS will be tested hierarchically in the following fixed order: * In the PD-L1-positive population; * In the mITT population
Duration of Objective Response (DoR) in China Population	Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)	DoR as determined by the investigator according to RECIST 1.1.
Percentage of Participants With Adverse Events	Baseline to end of study (approximately 58 months)
Maximum Serum Concentration (Cmax) of Atezolizumab	At pre-defined intervals from Day 1, Cycle 1 through Cycle 4 (cycle = 21 days)
Minimum Serum Concentration (Cmin) of Atezolizumab	At pre-defined intervals from Day 1, Cycle 1 through Cycle 4 (cycle = 21 days)
Incidence of Anti-Drug Antibodies (ADAs) to Atezolizumab	Baseline to end of study (approximately 58 months)
Overall Survival (OS) in mITT China Popluation	Baseline to end of study (approximately 58 months)	OS will be tested hierarchically in the following fixed order: * In the population with programmed deathligand 1 (PD-L1)-positive tumour status; * In the modified intent-to-treat (mITT) population
Proportion of Participants Alive 12 Months in China Population	Randomization to 12 months post randomization
Proportion of Participants Alive 18 Months in China Population	Randomization to 18 months post randomization
Progression Free Survival (PFS) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)	PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first.; PFS will be tested hierarchically in the following fixed order: * In the PD-L1-positive population; * In the mITT population
Confirmed Objective Response Rate (C-ORR) in China Population	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
Duration of Response for Confirmed Responders (C-DoR) in China Population	Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)

Trial Locations

Locations (136)

Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum; 🇩🇪 Essen, Germany

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Fundación CENIT para la Investigación en Neurociencias; 🇦🇷 Buenos Aires, Argentina

Instituto de Oncología de Rosario; 🇦🇷 Rosario, Argentina

The Valley Hospital; 🇺🇸 Paramus, New Jersey, United States

Clinical center University of Sarajevo; 🇧🇦 Sarajevo, Bosnia and Herzegovina

Bradford Hill Centro de Investigaciones Clinicas; 🇨🇱 Recoleta, Chile

Patagonia Research; 🇨🇱 Puerto Montt, Chile

Fundacion Arturo Lopez Perez; 🇨🇱 Santiago, Chile

Helsinki University Central Hospital; Dept of Oncology; 🇫🇮 Helsinki, Finland

Instituto Nacional de Cancerologia; Oncology; 🇲🇽 Mexico City, Mexico

Clinical Center of Montenegro; Clinic for Oncology and Radiotherapy; 🇲🇪 Podgorica, Montenegro

Clinique specialise Menara; Oncology Medical; 🇲🇦 Marrakech, Morocco

Oncology Institute of Vojvodina; 🇷🇸 Sremska Kamenica, Serbia

Centre Hospitalier Universitaire Mohamed VI; Oncologie-Hématologie; 🇲🇦 Marrakech, Morocco

Cancer Hospital , Chinese Academy of Medical; 🇨🇳 Beijing City, China

Hospital do Cancer de Pernambuco - HCP; 🇧🇷 Recife, PE, Brazil

Hospital Nossa Senhora da Conceicao; 🇧🇷 Porto Alegre, RS, Brazil

Hospital Araujo Jorge; Departamento de Ginecologia E Mama; 🇧🇷 Goiania, GO, Brazil

Jiangsu Province Hospital; 🇨🇳 Nanjing, China

Oncocentro Serviços Medicos E Hospitalares Ltda; 🇧🇷 Fortaleza, CE, Brazil

Instituto de Pesquisa Grupo NotreDame Intermedica; 🇧🇷 Sao Paulo, SP, Brazil

Hospital Provincial del Centenario; 🇦🇷 Rosario, Argentina

Peking University People's Hospital; 🇨🇳 Beijing, China

Beijing Cancer Hospital; 🇨🇳 Beijing, China

Clinica Vespucio; 🇨🇱 Santiago, Chile

Centro de Oncologia de Santa Catarina LTDA; 🇧🇷 Chapeco, SC, Brazil

Sun Yat-sen Memorial Hospital; 🇨🇳 Guangzhou, China

ONCOCENTRO APYS; Oncología; 🇨🇱 Vina Del Mar, Chile

Shanxi Province Cancer Hospital; 🇨🇳 Taiyuan City, China

Fudan University Shanghai Cancer Center; Medical Oncology; 🇨🇳 Shanghai City, China

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

the First Affiliated Hospital of Bengbu Medical College; 🇨🇳 Bengbu City, China

Fujian Medical University Union Hospital; 🇨🇳 Fuzhou City, China

The First Affiliated Hospital Of Jinzhou Medical University; 🇨🇳 Jinzhou City, China

The Affiliated Hospital of Medical College Qingdao University; 🇨🇳 Qingdao, China

SCRI Oncology Partners; 🇺🇸 Nashville, Tennessee, United States

Irccs Istituto Europeo Di Oncologia (IEO); Ricerca Di Senologia Medica; 🇮🇹 Milano, Lombardia, Italy

Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia; 🇮🇹 Firenze, Toscana, Italy

Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe; 🇩🇪 Hannover, Germany

Centre Eugene Marquis; Service d'oncologie; 🇫🇷 Rennes, France

Szent Margit Hospital; 🇭🇺 Budapest, Hungary

Shandong Cancer Hospital; 🇨🇳 Jinan, China

Florida Cancer Specialists - Fort Myers (Broadway); 🇺🇸 Fort Myers, Florida, United States

Florida Cancer Specialists & Research Institute; 🇺🇸 Saint Petersburg, Florida, United States

Magee-Woman's Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

Inova Schar Cancer Institute; 🇺🇸 Falls Church, Virginia, United States

Magee-Woman's Hospital; UPMC Pinnacle Cancer Center; 🇺🇸 Harrisburg, Pennsylvania, United States

University Clinical Center of the Republic of Srpska; 🇧🇦 Banja Luka, Bosnia and Herzegovina

Hospital Perola Byington; 🇧🇷 Sao Paulo, SP, Brazil

Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA; 🇧🇷 Sao Paulo, SP, Brazil

Hospital Sao Vicente de Paulo; 🇧🇷 Passo Fundo, RS, Brazil

James Lind Centro de Investigación Del Cáncer; 🇨🇱 Temuco, Chile

Jilin Cancer Hospital; 🇨🇳 Changchun, China

The First Affiliated Hospital, Chongqing Medical University; 🇨🇳 Chongqing, China

Sir Run Run Shaw Hospital Zhejiang University; 🇨🇳 Hangzhou City, China

Harbin Medical University Cancer Hospital; 🇨🇳 Harbin, China

Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province); 🇨🇳 Shijiazhuang, China

Tianjin Cancer Hospital; 🇨🇳 Tianjin, China

The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital); 🇨🇳 Xi'an, China

Hospital Hermanos Ameijeiras; 🇨🇺 La Habana, Cuba

Zhejiang Cancer Hospital; 🇨🇳 Zhejiang, China

Centre Georges-François Lecler; Ctr de Lutte Contre le Canc; 🇫🇷 Dijon, France

Instituto Nacional de Oncología y Radiología (INOR); 🇨🇺 La Habana, Cuba

Tampere University Hospital; Dept of Oncology; 🇫🇮 Tampere, Finland

Centre Leon Berard; Oncologie Genetique; 🇫🇷 Lyon, France

Institut Paoli-Calmettes; Oncologie Medicale 1; 🇫🇷 Marseille Cedex 09, France

Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque; 🇫🇷 Montpellier, France

INSTITUT CURIE_SITE PARIS - Service d'Oncologie Médicale.; 🇫🇷 St Cloud, France

Varisano Klinikum Frankfurt Höchst GmbH; 🇩🇪 Frankfurt, Germany

Centre Alexis Vautrin; Oncologie Medicale; 🇫🇷 Vandoeuvre-les-nancy, France

IGR; 🇫🇷 Villejuif, France

Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie; 🇩🇪 Halle, Germany

Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe; 🇩🇪 Dresden, Germany

Medizinisches Zentrum für Hämatologie und Onkologie; 🇩🇪 München, Germany

Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly; 🇭🇺 Budapest, Hungary

Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz;Sugarterapias Klinikai Onkologiai Intez; 🇭🇺 Miskolc, Hungary

Pécsi Tudományegyetem; Klinikai Központ Onkoterápiás Intézet; 🇭🇺 Pécs, Hungary

Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale; 🇮🇹 Napoli, Campania, Italy

Budapesti Uzsoki Utcai Kórház; 🇭🇺 Budapest, Hungary

Ospedale San Raffaele S.r.l.; 🇮🇹 Milano, Lombardia, Italy

Ospedale San Gerardo; 🇮🇹 Monza, Lombardia, Italy

Azienda Ospedaliero Universitaria San Martino; 🇮🇹 Genova, Liguria, Italy

Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico; 🇮🇹 Candiolo, Piemonte, Italy

Ospedale Antonio Perrino; Oncologia Medica; 🇮🇹 Brindisi, Puglia, Italy

IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda; 🇮🇹 Padova, Veneto, Italy

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Kazakh Scientific Research Institution Of Oncology and Radiology; 🇰🇿 Almaty, Kazakhstan

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

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

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Centro Medico Dalinde; 🇲🇽 Cdmx, Mexico CITY (federal District), Mexico

CENEIT Oncologicos; DENTRO DE CONDOMINIO SAN FRANCISCO; 🇲🇽 Mexico City, Mexico

Centre Hospitalier Universitaire Hassan II; 🇲🇦 FES, Morocco

Institut National D'oncologie Sidi Med Benabdellah; 🇲🇦 Rabat, Morocco

The Panama Clinic; 🇵🇦 Panama, Panama

?wi?tokrzyskie Centrum Onkologii; Dzia? Chemioterapii; 🇵🇱 Kielce, Poland

Instituto Nacional de Enfermedades Neoplasicas; 🇵🇪 Lima, Peru

Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr; 🇵🇱 Warszawa, Poland

Centro Hospitalar do Porto ? Hospital de Santo António; Oncologia; 🇵🇹 Porto, Portugal

Hospital de Santa Maria; Servico de Oncologia Medica; 🇵🇹 Lisboa, Portugal

City Clinical Oncology Dispensary, SPb SBIH CCOD; 🇷🇺 Saint-Petersburg, Sankt Petersburg, Russian Federation

FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"; 🇷🇺 Saint-Petersburg, Sankt Petersburg, Russian Federation

Moscow City Oncology Hospital #62; 🇷🇺 Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation

Moscow Clinical Scientific Center; 🇷🇺 Moscow, Moskovskaja Oblast, Russian Federation

FSBI "National Medical Research Center of Oncology N.N. Blokhin?; 🇷🇺 Moscow, Moskovskaja Oblast, Russian Federation

Institute of Oncology and Radiology of Serbia; 🇷🇸 Belgrade, Serbia

University Hospital Medical Center Bezanijska kosa; 🇷🇸 Belgrade, Serbia

Private Healthcare Institution Clinical Hospital RZhD Medicine; 🇷🇺 St. Petersburg, Sankt Petersburg, Russian Federation

Clinical Centre Nis, Clinic for Oncology; 🇷🇸 Nis, Serbia

National Cancer Centre; Medical Oncology; 🇸🇬 Singapore, Singapore

Wits Clinical Research; Charlotte Maxeke Johannesburg Academic Hospital; 🇿🇦 Johannesburg, South Africa

Medical Oncology Centre of Rosebank; Oncology; 🇿🇦 Johannesburg, South Africa

Private Oncology Centre; 🇿🇦 Pretoria, South Africa

Hospital de Cruces; Servicio de Oncologia; 🇪🇸 Bilbao, Vizcaya, Spain

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia; 🇪🇸 Madrid, Spain

Hospital Ramon y Cajal; Servicio de Oncologia; 🇪🇸 Madrid, Spain

Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia; 🇪🇸 Malaga, Spain

Hospital Clínico Universitario de Valencia; Servicio de Oncología; 🇪🇸 Valencia, Spain

Medipol University Medical Faculty; Oncology Department; 🇹🇷 Istanbul, Turkey

Hacettepe University Medical Faculty; Department of Internal Medicine; 🇹🇷 Ankara, Turkey

Ankara Oncology Hospital; Medical Oncology Department; 🇹🇷 Ankara, Turkey

Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi; 🇹🇷 Edirne, Turkey

Ege University Medical Faculty; Medical Oncology Department; 🇹🇷 Bornova, ?zm?r, Turkey

Velindre Cancer Centre; Oncology Dept; 🇬🇧 Cardiff, United Kingdom

University Hospital Coventry; 🇬🇧 Coventry, United Kingdom

Marmara University Pendik Training and Research Hospital; Medikal Onkoloji; 🇹🇷 Istanbul, Turkey

Necmettin Erbakan University Meram Medical Faculty ; Internal Diseases; 🇹🇷 Konya, Turkey

Western General Hospital; Edinburgh Cancer Center; 🇬🇧 Edinburgh, United Kingdom

Royal Lancaster Infirmary, Morecambe Bay Hospitals Nhs Trust; 🇬🇧 Lancaster, United Kingdom

Barts; 🇬🇧 London, United Kingdom

Guys and St Thomas NHS Foundation Trust, Guys Hospital; 🇬🇧 London, United Kingdom

Royal Stoke University Hospital; 🇬🇧 Stoke-on-Trent, United Kingdom

Christie Hospital NHS Trust; 🇬🇧 Manchester, United Kingdom

Mount Vernon Cancer Centre; 🇬🇧 Northwood, United Kingdom