BACKGROUND: Pembrolizumab plus lenvatinib is a treatment option for metastatic Renal Cell Carcinoma (mRCC). In the ARON-1 study we investigated we the real-world experiences gained from the use of this combination for mRCC. METHODS: We retrospectively investigated real-world clinical outcomes of mRCC patients receiving pembrolizumab plus lenvatinib within the ARON-1 study. Overall survival (OS) was calculated from the start of pembrolizumab plus lenvatinib to death for any cause. Progression-Free Survival (PFS) was defined as the time from the start of pembrolizumab to progression or death from any cause. Duration of response (DoR) was defined as the time from the start of pembrolizumab to disease progression or death, whichever occurred first, in patients who achieved complete remission (CR) or partial response (PR). Overall Response Rate (ORR) was defined as the proportion of patients who achieve a CR or PR per RECIST criteria. Adverse events were retrospectively collected from electronic and paper charts and categorized by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. RESULTS: Overall, we included 202 mRCC patients treated with pembrolizumab plus lenvatinib. The median follow-up time was 15.1 months. The median OS was not reached (NR), with a median PFS of 25.6 months and an Overall Response Rate (ORR) of 59%. The median Duration of Response (DoR) was 26.2 months. G3-G4 adverse events (AEs) were observed in 92 patients (46%), with hypertension being the most common AE (13%). CONCLUSIONS: Pembrolizumab plus lenvatinib is an effective and tolerable treatment for mRCC also in the real-world setting.

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

Centre for Cancer Translational and Clinical Research Institute Newcastle University Newcastle Upon Tyne UK

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 Universidad Panamericana Escuela de Medicina Mexico City Mexico

Department of Hematology and Oncology Sungkyunkwan University Samsung Medical Center Seoul South Korea

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Medical Oncology Faculty of Medicine Ankara University Ankara Turkey

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 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Department of Oncology Faculty of Medicine and Dentistry Palacký University Olomouc Czech Republic

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

Department of Urology Medical University of Innsbruck Innsbruck Austria

Department of Urology University Hospital Bonn Bonn Germany

Division of Medical Oncology Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari Piazzale G Cesare 11 70124 Bari Italy

Division of Medical Oncology Markey Cancer Center University of Kentucky Lexington KY USA

Division of Medical Oncology National Cancer Centre Singapore Singapore Singapore

Interdisciplinary Department of Medicine University of Bari A Moro Bari Italy

IRCCS Istituto Tumori Giovanni Paolo 2 70124 Bari Italy

IRCCS Ospedale Policlinico San Martino Genoa Italy

Latin American Cooperative Oncology Group LACOG Porto Alegre Brazil

Medical Oncology IRCCS Azienda Ospedaliero Universitaria di Bologna Bologna Italy

Medical Oncology Tawam Hospital Al Ain UAE

Medical Oncology Unit Macerata Hospital Macerata Italy

Medical Oncology Unit University Hospital of Parma Parma Italy

Oncology 1 Unit Department of Oncology Istituto Oncologico Veneto IOV IRCCS Padua Italy

Oncology and Hematology Department Hospital Sírio Libanês Brasília Brazil

Oncology Unit Hospital Israelita Albert Einstein São Paulo SP Brazil

Royal Marsden NHS Foundation Trust London UK

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