Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial.

CheckMate 025 has shown superior efficacy for nivolumab over everolimus in patients with advanced renal cell carcinoma (aRCC) along with improved safety and tolerability. This analysis assesses the long-term clinical benefits of nivolumab versus everolimus.

The randomized, open-label, phase 3 CheckMate 025 trial (NCT01668784) included patients with clear cell aRCC previously treated with 1 or 2 antiangiogenic regimens. Patients were randomized to nivolumab (3 mg/kg every 2 weeks) or everolimus (10 mg once a day) until progression or unacceptable toxicity. The primary endpoint was overall survival (OS). The secondary endpoints were the confirmed objective response rate (ORR), progression-free survival (PFS), safety, and health-related quality of life (HRQOL).

Eight hundred twenty-one patients were randomized to nivolumab (n = 410) or everolimus (n = 411); 803 patients were treated (406 with nivolumab and 397 with everolimus). With a minimum follow-up of 64 months (median, 72 months), nivolumab maintained an OS benefit in comparison with everolimus (median, 25.8 months [95% CI, 22.2-29.8 months] vs 19.7 months [95% CI, 17.6-22.1 months]; hazard ratio [HR], 0.73; 95% CI, 0.62-0.85) with 5-year OS probabilities of 26% and 18%, respectively. ORR was higher with nivolumab (94 of 410 [23%] vs 17 of 411 [4%]; P < .001). PFS also favored nivolumab (HR, 0.84; 95% CI, 0.72-0.99; P = .0331). The most common treatment-related adverse events of any grade were fatigue (34.7%) and pruritus (15.5%) with nivolumab and fatigue (34.5%) and stomatitis (29.5%) with everolimus. HRQOL improved from baseline with nivolumab but remained the same or deteriorated with everolimus.

The superior efficacy of nivolumab over everolimus is maintained after extended follow-up with no new safety signals, and this supports the long-term benefits of nivolumab monotherapy in patients with previously treated aRCC.

CheckMate 025 compared the effects of nivolumab (a novel immunotherapy) with those of everolimus (an older standard-of-care therapy) for the treatment of advanced kidney cancer in patients who had progressed on antiangiogenic therapy. After 5 years of study, nivolumab continues to be better than everolimus in extending the lives of patients, providing a long-lasting response to treatment, and improving quality of life with a manageable safety profile. The results demonstrate that the clinical benefits of nivolumab versus everolimus in previously treated patients with advanced kidney cancer continue in the long term.

Cancer. 2020 Jul 16 [Epub ahead of print]

Robert J Motzer, Bernard Escudier, Saby George, Hans J Hammers, Sandhya Srinivas, Scott S Tykodi, Jeffrey A Sosman, Elizabeth R Plimack, Giuseppe Procopio, David F McDermott, Daniel Castellano, Toni K Choueiri, Frede Donskov, Howard Gurney, Stéphane Oudard, Martin Richardet, Katriina Peltola, Ajjai S Alva, Michael Carducci, John Wagstaff, Christine Chevreau, Satoshi Fukasawa, Yoshihiko Tomita, Thomas C Gauler, Christian K Kollmannsberger, Fabio A Schutz, James Larkin, David Cella, M Brent McHenry, Shruti Shally Saggi, Nizar M Tannir

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Department of Medical Oncology, Gustave Roussy, Villejuif, France., Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York., Division of Hematology and Oncology, UT Southwestern Kidney Cancer Program, Dallas, Texas., Stanford Cancer Institute, Stanford University Medical Center, Stanford, California., Department of Medicine, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington., Department of Hematology/Oncology, Northwestern University Medical Center, Chicago, Illinois., Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania., Fondazione Istituto Nazionale Tumori, Milan, Italy., Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts., Oncologia Medica, Hospital Universitario 12 De Octubre, Madrid, Spain., Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Department of Oncology, Aarhus University Hospital, Aarhus, Denmark., Department of Medical Oncology, Westmead Hospital and Macquarie University, Westmead, New South Wales, Australia., Service de Cancérologie Médicale, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France., Fundacion Richardet Longo, Instituto Oncologico de Cordoba, Cordoba, Argentina., Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland., Division of Hematology and Oncology, University of Michigan, Ann Arbor, Michigan., Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, Maryland., South West Wales Cancer Institute and Swansea University College of Medicine, Swansea, United Kingdom., Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France., Prostate Center and Division of Urology, Chiba Cancer Center, Chiba, Japan., Department of Urology, Department of Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Department of Medicine, University Hospital Essen, University of Duisburg-Essen, Duisburg, Germany., Division of Medical Oncology, BC Cancer-Vancouver Cancer Centre, Vancouver, British Columbia, Canada., Beneficencia Portuguesa de São Paulo, São Paulo, Brazil., Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom., Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Department of Biostatistics, Bristol Myers Squibb, Princeton, New Jersey., Department of Clinical Trials, Bristol Myers Squibb, Princeton, New Jersey., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.