INTRODUCTION: Four approved immune-based combinations for untreated metastatic renal carcinoma have demonstrated survival benefits. The ARON-1 study (NCT05287464) analyzed real-world data of patients with metastatic renal cell carcinoma receiving first-line immuno-oncology combinations. This sub-analysis is focused on the nivolumab plus cabozantinib effectiveness. METHODS: We conducted a retrospective study across 52 centers in 17 countries, including patients with metastatic renal carcinoma treated with first-line nivolumab plus cabozantinib, regardless of histologic characteristics, performance status, or risk by IMDC prognostic model. Patients with incomplete medical data were excluded. The primary objective of this sub-analysis of the ARON-1 study was to evaluate the real-world effectiveness and safety. RESULTS: A total of 333 patients were treated with nivolumab plus cabozantinib, clinical characteristics included ECOG performance status ≥2 20%, non-clear cell histology 16%, sarcomatoid de-differentiation 12%, and poor-risk by IMDC 28%. At a median follow-up of 15.9 months (95%CI 11.2-44.0), the median overall survival was not reached (40.0-NR), the probability of survival at 2 years was 75%, while median progression free survival was 33.7 months (95%CI 21.1-38.9). In the entire cohort, an objective response was observed in 58%, with 6% complete responses, and a median duration of response of 38.9 months (95%CI 33.7-NR). At multivariate analysis, adverse prognostic factors for overall survival included ECOG performance status ≥2, sarcomatoid de-differentiation, brain and bone metastases, and poor IMDC group. In the safety analysis, the incidence of grade 3 or higher toxicity was 37%, with hypertension and hand-foot syndrome being the most frequent adverse events. CONCLUSION: The findings in the present real-world study reaffirm the clinical benefits and safety of the nivolumab plus cabozantinib combination across all subgroups, including populations that are generally excluded from clinical trials for whom data is often missing. Poor performance status, sarcomatoid de-differentiation, bone or central nervous system metastases and IMDC poor risk group were confirmed as negative prognostic factors.

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

Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czechia

Clinical Oncology Sociedad de Oncología y Hematología del Cesar Valledupar Colombia

Department of Hemato Oncology Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Mexico City Mexico

Department of Hematology Oncology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Medical Oncology Ankara University Faculty of Medicine Ankara Türkiye

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

Department of Medical Oncology Fundacion Instituto Valenciano de Oncologia Valencia Spain

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 MD Anderson Cancer Center Madrid Madrid Spain

Department of Medicine and Surgery University of Parma Parma Italy

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

Department of Oncology Faculty of Medicine and Dentistry Palacký University Olomouc Czechia

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

Division of Medical Oncology Department of Internal Medicine University of Kansas Cancer Center Westwood KS United States

Escuela de Medicina Universidad Panamericana Mexico City Mexico

Genitourinary Cancer Group Latin American Cooperative Oncology Group LACOG Porto Alegre Brazil

Hematology Oncology Department Faculty of Medicine Saint Joseph University of Beirut Beirut Lebanon

Medical Oncology Department CHU Insular Materno Infantil Las Palmas de Gran Canaria Spain

Medical Oncology IRCCS Azienda Ospedaliero Universitaria di Bologna Bologna Italy

Medical Oncology Tawam Hospital Al Ain United Arab Emirates

Medical Oncology Unit Macerata Hospital Macerata Italy

Medical Oncology Unit University Hospital of Parma Parma Italy

Oncology and Hematology Department Hospital Sírio Libanês Brasília Brazil

Oncology Institute Haifa Israel

Oncology Unit 2 University Hospital of Pisa Pisa Italy

Royal Marsden NHS Foundation Trust London United Kingdom

The Institute of Cancer Research London United Kingdom

Translational and Clinical Research Institute Centre for Cancer Newcastle University Newcastle upon Tyne United Kingdom

Unit of Medical Oncology and Biomolecular Therapy and C R E A T E Center for Research and Innovation Medicine Department of Medical and Surgical Sciences University of Foggia Policlinico Riuniti Foggia Italy

UOC Oncologia Territoriale Ausl Latina Aprilia Italy

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