Conditional survival estimates provide critical prognostic information for patients with advanced renal cell carcinoma (aRCC). Efficacy, safety, and conditional survival outcomes were assessed in CheckMate 214 (ClinicalTrials.
gov identifier NCT02231749) with a minimum follow-up of 5 years.
Patients with untreated aRCC were randomized to receive nivolumab (NIVO) (3 mg/kg) plus ipilimumab (IPI) (1 mg/kg) every 3 weeks for 4 cycles, then either NIVO monotherapy or sunitinib (SUN) (50 mg) daily (four 6-week cycles). Efficacy was assessed in intent-to-treat, International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk/poor-risk, and favorable-risk populations. Conditional survival outcomes (the probability of remaining alive, progression free, or in response 2 years beyond a specified landmark) were analyzed.
The median follow-up was 67.7 months; overall survival (median, 55.7 vs 38.4 months; hazard ratio, 0.72), progression-free survival (median, 12.3 vs 12.3 months; hazard ratio, 0.86), and objective response (39.3% vs 32.4%) benefits were maintained with NIVO+IPI versus SUN, respectively, in intent-to-treat patients (N = 550 vs 546). Point estimates for 2-year conditional overall survival beyond the 3-year landmark were higher with NIVO+IPI versus SUN (intent-to-treat patients, 81% vs 72%; intermediate-risk/poor-risk patients, 79% vs 72%; favorable-risk patients, 85% vs 72%). Conditional progression-free survival and response point estimates were also higher beyond 3 years with NIVO+IPI. Point estimates for conditional overall survival were higher or remained steady at each subsequent year of survival with NIVO+IPI in patients stratified by tumor programmed death ligand 1 expression, grade ≥3 immune-mediated adverse event experience, body mass index, and age.
Durable clinical benefits were observed with NIVO+IPI versus SUN at 5 years, the longest phase 3 follow-up for a first-line checkpoint inhibitor-based combination in patients with aRCC. Conditional estimates indicate that most patients who remained alive or in response with NIVO+IPI at 3 years remained so at 5 years.
Cancer. 2022 Apr 05 [Epub ahead of print]
Robert J Motzer, David F McDermott, Bernard Escudier, Mauricio Burotto, Toni K Choueiri, Hans J Hammers, Philippe Barthélémy, Elizabeth R Plimack, Camillo Porta, Saby George, Thomas Powles, Frede Donskov, Howard Gurney, Christian K Kollmannsberger, Marc-Oliver Grimm, Carlos Barrios, Yoshihiko Tomita, Daniel Castellano, Viktor Grünwald, Brian I Rini, M Brent McHenry, Chung-Wei Lee, Jennifer McCarthy, Flavia Ejzykowicz, Nizar M Tannir
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Division of Medical Oncology, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts., Department of Medical Oncology, Gustave Roussy, Villejuif, France., Bradford Hill Clinical Research Center, Santiago, Chile., Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts., Department of Medical Oncology, University of Texas Southwestern Kidney Cancer Program, Dallas, Texas., Medical Oncology, Strasbourg European Cancer Institute, Strasbourg, France., Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania., Department of Internal Medicine, University of Pavia, Pavia, Italy., Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York., Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Center, Queen Mary University of London, Royal Free National Health Service Trust, London, United Kingdom., Department of Oncology, Aarhus University Hospital, Aarhus, Denmark., Department of Medical Oncology, Westmead Hospital and Macquarie University, Sydney, New South Wales, Australia., Department of Medicine, British Columbia Cancer Agency, Vancouver, British Columbia, Canada., Department of Urology, Jena University Hospital, Jena, Germany., Oncology Research Unit, Saint Luke Hospital, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil., Departments of Urology and Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Medical Oncology Department, October 12th University Hospital, Cancer Network Biomedical Research Center, Madrid, Spain., Interdisciplinary Genitourinary Oncology, West German Cancer Center Clinic for Internal Medicine and Clinic for Urology, University Hospital Essen, Essen, Germany., Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, Tennessee., Department of Biostatistics, Bristol Myers Squibb, Princeton, New Jersey., Department of Clinical Trials, Bristol Myers Squibb, Princeton, New Jersey., Department of Clinical Scientists, Bristol Myers Squibb, Princeton, New Jersey., Department of Health Economics and Outcomes Research, Bristol Myers Squibb, Princeton, New Jersey., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.