Non-clear cell renal cell carcinoma (nccRCC) lacks direct comparisons of immune-based combinations, presenting an unmet need for defining optimal treatment for this specific population. This study aimed to assess the real-world efficacy of immune-based combinations in intermediate-/poor-risk nccRCC.
We conducted a multicenter, retrospective study of patients (≥18 yr) with metastatic nccRCC treated with first-line immune-based combinations across 56 centers in 17 countries between January 2021 and December 2024. Patients received pembrolizumab/lenvatinib, pembrolizumab/axitinib, nivolumab/cabozantinib, or nivolumab/ipilimumab. The primary endpoints were overall survival (OS) and progression-free survival (PFS), analyzed using Kaplan-Meier and Cox proportional-hazard models, and overall response rate (ORR) evaluated as per RECIST 1.1 criteria.
Among the 323 patients analyzed (median follow-up: 21.2 mo), the median OS was 31.1 mo (95% confidence interval [CI] 24.6-40.4), with a 2-yr OS rate of 58%. The ORR was 38% (2% complete response and 36% partial response), and the median PFS was 13.0 mo (95% CI 10.0-17.4). Immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) significantly outperformed ICI doublets across efficacy metrics. Limitations include retrospective design and a selection bias.
Our analysis suggests ICI/TKI combinations as the optimal strategy for intermediate-/poor-risk nccRCC, with pembrolizumab/lenvatinib showing marked benefits. Further studies are needed to validate these findings.
European urology focus. 2025 Jul 29 [Epub ahead of print]
Francesco Massari, Veronica Mollica, Ray Manneh Kopp, Enrique Grande, Ondřej Fiala, Ravindran Kanesvaran, Haoran Li, Timothy J Schieber, Maria José Juan Fita, Alexandr Poprach, Cristian Lolli, Maria T Bourlon, Alfonso Gómez de Liaño, Francesco Grillone, Kaisa Sunela, Alessandro Rizzo, Marwan Ghosn, Linda Cerbone, Tarek Taha, Yüksel Ürün, Javier Molina-Cerrillo, Teresa Alonso-Gordoa, Edoardo Lenci, Inmaculada Orejana Martin, Hussam Abu-Sini, Pasquale Rescigno, Dipen Bhuva, Andre Poisl Fay, Vincenza Conteduca, Ahmet Yildirim, Matteo Rosellini, Umut Akova, Elisa Tassinari, Hatice Bölek, Andrey Soares, Fernando Sabino Marques Monteiro, Sebastiano Buti, Mehmet Asim Bilen, Matteo Santoni
Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. Electronic address: ., Clinical oncology, Sociedad de Oncología y Hematología del Cesar, Valledupar, Colombia., Department of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain., Department of Oncology and Radiotherapeutics, Faculty of Medicine, University Hospital in Pilsen, Charles University, Pilsen, Czech Republic; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic., Division of Medical Oncology, National Cancer Centre Singapore, Singapore., Division of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, Westwood, KS, USA., Medical Oncology, Fundación Instituto Valenciano de Oncología, Valencia, Spain., Masaryk Memorial Cancer Institute, Brno, Czech Republic; Faculty of Medicine, Masaryk University, Brno, Czech Republic., Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy., Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Medical Oncology Department, CHU Insular-Materno Infantil, Las Palmas, Spain., Medical Oncology Unit, Presidio Ospedaliero Pugliese Ciaccio, Azienda Ospedaliera Universitaria "Renato Dulbecco", Catanzaro, Italy., Department of Oncology, Tampere Cancer Center, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University, Tampere, Finland., S.S.D. C.O.r.O. Bed Management Presa in Carico, TDM, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy., Hematology-Oncology Department, Faculty of Medicine, Saint Joseph University of Beirut, Beirut, Lebanon., Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy., The Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK., Medical Oncology, Ankara University Medical Faculty, Ankara, Turkey., Medical Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain., Medical Oncology Unit, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Pesaro, Italy., Oncology Institute, Rambam Healthcare campus, Haifa, Israel., Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK., Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India., PUCRS School of Medicine, Porto Alegre, RS, Brazil., Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Policlinico Riuniti, Foggia, Italy., Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA., Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil; Hospital Israelita Albert Einstein, São Paulo, SP, Brazil., Latin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil; Hospital Sírio-Libanês, Brasília, DF, Brazil., Medical Oncology Unit, University Hospital of Parma, Parma, Italy; Department of Medicine and Surgery, University of Parma, Parma, Italy., Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute of Emory University, Atlanta, GA, USA., Medical Oncology Unit, Macerata Hospital, Macerata, Italy.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/40738794