The optimal first-line therapy for metastatic renal cell carcinoma (mRCC) remains uncertain, despite recent advancements in immune-based combinations. This retrospective study compares the effectiveness of pembrolizumab plus axitinib (PA) and nivolumab plus cabozantinib (NC) as first-line treatments for mRCC in a real-world setting.
Patient data were collected from 55 centers across 16 countries, encompassing individuals diagnosed with mRCC receiving first-line treatment with PA or NC between January 2016 and October 2023. Clinical and tumor features and treatment responses were recorded. The primary endpoints were overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to second progression. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazard models, and chi-square tests.
A total of 760 patients with a median age of 64 years (range, 29-88) were included. Of them, 607 received PA, and only 153 NC. In the overall study population, ORR was 59% for and 49% for PA. Median OS was 55.7 months and not reached (NR) for PA and NC, respectively (P = .51), while median PFS was longer with NC (27.6 months) than for PA (16.2 months, P = .003). Subgroup analysis suggested a PFS benefits for NC in male, younger patients, intermediate risk group, clear cell histology, and lung involvement, as well as ORR favored NC in good risk patients. Multivariate analysis identified first-line therapy as a significant factor associated with PFS.
In this certainly biased retrospective comparison, NC demonstrated superior ORR and longer PFS compared to PA in mRCC. These findings underscore the importance of considering individual patient characteristics and risk profiles when selecting first-line therapy for mRCC.
Cancer immunology, immunotherapy : CII. 2025 May 27*** epublish ***
Matteo Santoni, Giandomenico Roviello, Enrique Grande, Ugo De Giorgi, Ondrej Fiala, Emmanuel Seront, Javier Molina-Cerrillo, Renate Pichler, Zin W Myint, Jakub Kucharz, Ravindran Kanesvaran, Thomas Büttner, Martin Pichler, Umberto Basso, Jindrich Kopecky, Maria T Bourlon, Linda Cerbone, Tomas Buchler, Alvaro Pinto, Alfonso Gómez de Liaño, Caterina Gianni, Anca Zgura, Pasquale Rescigno, Jawaher Ansari, Orazio Caffo, Zsófia Küronya, Maria Giuseppa Vitale, Dipen Bhuva, Martina Catalano, Nuno Vau, Ray Manneh Kopp, Sebastiano Buti, Aristotelis Bamias, Camillo Porta, Kaisa Sunela, Francesco Massari
Oncology Unit, Macerata Hospital, Macerata, Italy., Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy. ., Department of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain., Department of Medical Oncology, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, Italy., Department of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic., Department of Medical Oncology, Cliniques Universitaires Saint-Luc 1200, Brussels, Belgium., Hospital Ramón y Cajal, Madrid, Spain., Department of Urology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria., Markey Cancer Center, University of Kentucky, Lexington, KY, 40536-0293, USA., Department of Uro-Oncology, Maria Sklodowska-Curie National Research Institute of Oncology Warsaw, Warsaw, Poland., Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore., Department of Urology, University Hospital Bonn (UKB), 53127, Bonn, Germany., Division of Oncology, Department of Internal Medicine, Medical University of Graz, Augenbruggerplatz 15, 8010, Graz, Austria., Oncology 3 Unit, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padua, Italy., Department of Clinical Oncology and Radiotherapy, University Hospital Hradec Kralove, Hradec Kralove, Czechia., Hematology and Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy., Department of Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital Prague, Prague, Czech Republic., Medical Oncology Department, La Paz University Hospital, Madrid, Spain., Medical Oncology Department, CHU Insular-Materno Infantil, Las Palmas de Gran Canaria, Spain., Department of Obstetrics-Radiotherapy, Alexandru Trestioreanu Institute of Oncology, "Carol Davila" University of Medicine and Pharmacy, Prof. Dr, Bucharest, Romania., Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle Upon Tyne, UK., Medical Oncology, Tawam Hospital, Al Ain, United Arab Emirates., Medical Oncology Unit, Santa Chiara Hospital, Trento, Italy., Department of Genitourinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology, Budapest, Hungary., Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy., Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India., Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy., Urologic Oncology, Champalimaud Clinical Center, 1400-038, Lisbon, Portugal., Clinical Oncology, Sociedad de Oncología y Hematología del Cesar, Valledupar, Colombia., Medical Oncology Unit, University Hospital of Parma, 43126, Parma, Italy., 2nd Propaedeutic Department of Internal Medicine, School of Medicine, ATTIKON University Hospital, National and Kapodistrian University of Athens, Athens, Greece., Interdisciplinary Department of Medicina, University of Bari "Aldo Moro" and Division of Medical Oncology, A.O.U. Consorziale Policlinico Di Bari, Bari, Italy., Finnish Medicines Agency Fimea, Tampere, Finland., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Via Albertoni, 15, Bologna, Italy.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/40423789