Longer follow-up and new trial data from phase 3 randomised controlled trials investigating immune checkpoint blockade (PD-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) have recently become available. The CheckMate 9ER trial demonstrated an improved progression-free survival (PFS) and overall survival (OS) benefit for the combination of cabozantinib plus nivolumab. A Keynote-426 update demonstrated an ongoing OS benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups, while an update of CheckMate 214 confirmed the long-term benefit of ipilimumab plus nivolumab in IMDC intermediate and poor risk patients. The RCC Guidelines Panel continues to recommend these tyrosine kinase inhibitors + immunotherapy (IO) combination across IMDC risk groups in advanced first-line RCC and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate and poor risk. PATIENT SUMMARY: New data from trials of immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit with the combination of cabozantinib plus nivolumab and pembrolizumab plus axitinib and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.

Academic Urology Unit University of Aberdeen Aberdeen UK; Department of Urology Aberdeen Royal Infirmary Aberdeen UK

Department of Cancer Medicine Gustave Roussy Université Paris Saclay Villejuif France

Department of Nephrology and Hypertension University Medical Center Utrecht Utrecht The Netherlands; Patient Advocate International Kidney Cancer Coalition Utrecht The Netherlands

Department of Surgical and Perioperative Sciences Urology and Andrology Umeå University Umeå Sweden

Department of Translational Medicine Division of Urological Cancers Lund University Malmö Sweden

Department of Urology Cabueñes University Hospital Gijón Spain

Department of Urology Chaim Sheba Medical Center Tel Hashomer Ramat Gan Israel

Department of Urology Coimbra University Hospital Coimbra Portugal

Department of Urology Darent Valley Hospital Dartford and Gravesham NHS Trust Dartford UK

Department of Urology Elbe Kliniken Stade Germany

Department of Urology Royal Bournemouth Hospital Bournemouth UK; Department of Surgery University of Cambridge Cambridge UK

Department of Urology San Raffaele Scientific Institute Milan Italy; Division of Experimental Oncology Unit of Urology Urological Research Institute IRCCS San Raffaele Hospital Milan Italy

Department of Urology Sunderby Sjukhus Umeå University Luleå Sweden

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

Department of Urology University Hospital Tuebingen Tuebingen Germany; German Cancer Consortium Heidelberg Germany

Department of Urology University of Eastern Piedmont Maggiore della Carità Hospital Novara Italy

The Royal Free London NHS Foundation Trust London UK; UCL Division of Surgery and Interventional Science University College London London UK; Department of Urology The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands

The Royal Free NHS Trust and Barts Cancer Institute Queen Mary University of London London UK

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