Metastatic renal cell carcinoma (mRCC) carrying sarcomatoid features (sRCC) has aggressive biology and poor prognosis. First-line immunotherapy (IO)-based combinations have improved the outcome of clear cell RCC patients, including that of sRCC. Real-world data confirming the adequate first-line management of sRCC is largely lacking. We investigated the clinical features and the outcome of sRCC patients treated with IO-based combinations within the ARON-1 study population (NCT05287464). The primary objective was to define the incidence and baseline clinical characteristics of sRCC compared with non-sRCC patients. The secondary objective was to describe the outcome of sRCC patients based on type of first-line treatment (IO + IO vs. IO + tyrosin kinase inhibitor [TKI]). We identified 1362 mRCC patients with IMDC intermediate or poor risk, 226 sRCC and 1136 non-sRCC. These two subgroups did not differ in terms of baseline characteristics. The median overall survival (OS) was 26.8 months (95%CI 21.6-44.2) in sRCC and 35.3 months (95%CI 30.2-40.4) in non-sRCC patients (p = .013). The median progression-free survival (PFS) was longer in non-sRCC patients compared to sRCC (14.5 vs. 12.3 months, p = .064). In patients treated with first-line IO + TKI the median OS was 34.4 months compared to 26.4 months of those who received IO + IO (p = .729). The median PFS was 12.4 months with IO + TKI and 12.3 months with IO + IO (p = .606). In conclusion, we confirm that sRCC are aggressive tumors with poor prognosis. IO-based combinations improve survival outcomes of sRCC patients, regardless from the type of strategy (IO + IO versus IO + TKI) adopted.

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

Clinical Oncology Sociedad de oncología y hematología del Cesar Valledupar Colombia

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 Florence Italy

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Medical Oncology AUSL della Romagna Ospedale Civile degli Infermi Faenza Italy

Department of Medical Oncology Hospital Ramón y Cajal Madrid Spain

Department of Medical Oncology MD Anderson Cancer Center Madrid Madrid Spain

Department of Medical Oncology San Camillo Forlanini Hospital Rome Italy

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

Department of Oncology Tampere University Hospital Tampere Cancer Center Faculty of Medicine and Health Technology Tampere University Tampere Finland

Department of Urology Medical University of Innsbruck Innsbruck Austria

Department of Urology University Hospital Bonn Bonn Germany

Division of Medical Oncology A O U Consorziale Policlinico Di Bari Bari Italy

Division of Oncology Department of Internal Medicine Medical University of Graz Graz Austria

Division of Oncology Department of Oncology and Hematology University Hospital of Modena Modena Italy

Medical Oncology Aprilia Hospital Latina Italy

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 National Cancer Centre Singapore Singapore Singapore

Medical Oncology Niguarda Cancer Center Grande Ospedale Metropolitano Niguarda Milan Italy

Medical Oncology Tawam Hospital Al Ain UAE

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

Medical Oncology Unit Fondazione Policlinico A Gemelli IRCCS Rome Italy

Oncologia Oncologia PO Pugliese Ciaccio Azienda Ospedaliera Universitaria Renato Dulbecco Catanzaro Italy

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

Oncology and Hematology Department Hospital Sírio Libanê Brasília Brazil

Oncology Department Candiolo Cancer Institute IRCCS FPO Torino Italy

Oncology Operative Unit Santa Maria delle Grazie Hospital Pozzuoli Italy

Oncology Unit 2 University Hospital of Pisa Pisa Italy

Oncology Unit Macerata Hospital Macerata Italy

Section of Innovation Biomedicine Oncology Area Department of Engineering for Innovation Medicine of Verona Verona Italy

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