BACKGROUND: Immuno-oncology combinations have achieved survival benefits in patients with metastatic renal cell carcinoma (mRCC). OBJECTIVE: The ARON-1 study (NCT05287464) was designed to globally collect real-world data on the use of immuno-combinations as first-line therapy for mRCC patients. PATIENTS AND METHODS: Patients aged ≥ 18 years with a cytologically and/or histologically confirmed diagnosis of mRCC treated with first-line immuno-combination therapies were retrospectively included from 47 International Institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall clinical benefit (OCB). RESULTS: A total of 729 patients were included; tumor histology was clear-cell RCC in 86% of cases; 313 patients received dual immuno-oncology (IO + IO) therapy while 416 were treated with IO-tyrosine kinase inhibitor (IO + TKI) combinations. In the overall study population, the median OS and PFS were 36.5 and 15.0 months, respectively. The median OS was longer with IO+TKI compared with IO+IO therapy in the 616 patients with intermediate/poor International mRCC Database Consortium (IMDC) risk criteria (55.7 vs 29.7 months; p = 0.045). OCB was 84% for IO+TKI and 72% for IO + IO combination (p < 0.001). CONCLUSIONS: Our study may suggest that immuno-oncology combinations are effective as first-line therapy in the mRCC real-world context, showing outcome differences between IO + IO and IO + TKI combinations in mRCC subpopulations. CLINICAL TRIAL REGISTRATION: NCT05287464.

2nd Propaedeutic Department of Internal Medicine School of Medicine ATTIKON University Hospital National and Kapodistrian University of Athens Athens Greece

Chair of Oncology Interdisciplinary Department of Medicine University of Bari Aldo Moro Bari Italy

Department of Biomedical Sciences Humanitas University Pieve Emanuele Milan Italy

Department of Clinical Oncology and Radiotherapy University Hospital Hradec Kralove Hradec Kralove Czech Republic

Department of Genitourinary Medical Oncology and Clinical Pharmacology National Institute of Oncology Budapest Hungary

Department of Health Sciences Section of Clinical Pharmacology and Oncology University of Florence Viale Pieraccini 6 50139 Florence Italy

Department of Internal Medicine and Medical Specialties University of Genoa Genoa Italy

Department of Internal Medicine Hematology Oncology Ochsner Medical Center New Orleans LA USA

Department of Medical Oncology Army Hospital Research and Referral New Delhi India

Department of Medical Oncology Centre Hospitalier de Jolimont Haine Saint Paul Belgium

Department of Medical Oncology Hospital Ramón y Cajal Madrid Spain

Department of Medical Oncology IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori Meldola Italy

Department of Medical Oncology Maggiore della Carità University Hospital 28100 Novara Italy

Department of Medical Oncology MD Anderson Cancer Center Madrid Madrid Spain

Department of Medical Oncology Università Politecnica delle Marche AOU Ospedali Riuniti delle Marche Ancona Italy

Department of Oncology 1st Faculty of Medicine Charles University Thomayer University Hospital 14059 Prague Czech Republic

Department of Oncology and Radiotherapeutics Faculty of Medicine University Hospital in Pilsen Charles University Pilsen Czech Republic

Department of Oncology IRCCS Humanitas Research Hospital Rozzano Milan Italy

Department of Oncology Radiotherapy Prof Dr Alexandru Trestioreanu Institute of Oncology Carol Davila University of Medicine and Pharmacy Bucharest Romania

Department of Oncology San Camillo Forlanini Hospital Rome Italy

Department of Radiological Oncological and Anatomo Pathological Science Sapienza University of Rome Viale Regina Elena 324 00185 Rome Italy

Department of Surgical Oncological and Oral Sciences Section of Medical Oncology University of Palermo Palermo Italy

Department of Uro oncology Maria Sklodowska Curie National Research Institute of Oncology Warsaw Poland

Department of Urology Medical University of Innsbruck Anichstrasse 35 6020 Innsbruck Austria

Department of Urology University Hospital Bonn 53127 Bonn Germany

Dipartimento di Oncologia Medica Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy

Division of Medical Oncology A O U Consorziale Policlinico di Bari Piazza G Cesare 11 70124 Bari Italy

Division of Medical Oncology National Cancer Centre Singapore Singapore Singapore

Division of Oncology Department of Internal Medicine Medical University of Graz Augenbruggerplatz 15 8010 Graz Austria

Hematology and Oncology Department Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico

IRCCS Ospedale Policlinico San Martino Genoa Italy

Latin American Cooperative Oncology Group LACOG Porto Alegre Brazil

Markey Cancer Center University of Kentucky Lexington KY 40536 0293 USA

Medical Oncology 1 IRCCS Regina Elena National Cancer Institute Rome Italy

Medical Oncology Department La Paz University Hospital Madrid Spain

Medical Oncology Division of Urogenital and Head and Neck Tumours IEO European Institute of Oncology IRCCS Milan Italy

Medical Oncology IRCCS Azienda Ospedaliero Universitaria di Bologna Via Albertoni 15 Bologna Italy

Medical Oncology Ospedale San Paolo 17100 Savona Italy

Medical Oncology Tawam Hospital Al Ain United Arab Emirates

Medical Oncology Unit Department of Medicine and Surgery University Hospital of Parma University of Parma Parma Italy

Medical Oncology Unit Santa Chiara Hospital Trento Italy

Molecular Medicine and Cell Therapy Foundation Polytechnic University of the Marche Region 60126 Ancona Italy

Oncologia Medica Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy

Oncologia Medica Ospedale Maggiore di Cremona Cremona Italy

Oncology 3 Unit Department of Oncology Istituto Oncologico Veneto IOV IRCCS Padua Italy

Oncology and Hematology Department Hospital Santa Lucia SHLS 716 Cj C Brasília DF 70390 700 Brazil

Oncology Candiolo Cancer Institute IRCCS FPO 10060 Turin Italy

Oncology Unit 2 University Hospital of Pisa 56126 Pisa Italy

Oncology Unit A R N A S Civico Palermo Italy

Oncology Unit Macerata Hospital Via Santa Lucia 2 62100 Macerata Italy

Section of Oncology Department of Medicine University of Verona School of Medicine Verona University Hospital Trust Verona Italy

Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico Don Tonino Bello 1 R C C S Istituto Tumori Giovanni Paolo 2 Viale Orazio Flacco 65 70124 Bari Italy

Unità di Oncologia Medica Azienda Ospedaliero Universitaria di Cagliari Cagliari Italy

UOC di Oncologia Azienda Ospedaliera di Rilievo Nazionale Cardarelli di Napoli Naples Italy

UOC Oncologia Azienda Ospedaliera Ospedali Riuniti Marche Nord Tuscany Italy

Urologic Oncology Champalimaud Clinical Center 1400 038 Lisbon Portugal

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ClinicalTrials.gov
NCT05287464