Three-Year Efficacy and Safety Update From the Phase III CheckMate 025 Study of Nivolumab Versus Everolimus in Patients With Advanced Renal Cell Carcinoma (aRCC)


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Padmanee Sharma1,Scott S Tykodi2,Bernard Escudier3,Michael Carducci4,Stephane Oudard5,Hans J. Hammers4,Saby George6,Daniel Castellano7,Ajjai S. Alva8,Martin E Richardet9,Christine Chevreau10,Elizabeth R. Plimack11,Sandhya Srinivas12,Giuseppe Procopio13,Jeffrey A. Sosman14,David F. McDermott15,Toni K. Choueiri16,Elmer Berghorn17,Lingfeng Yang17,Robert J. Motzer18,John Wagstaff19
1MD Anderson Cancer Center,2University of Washington and Fred Hutchinson Cancer Research Center,3Gustave Roussy,4Johns Hopkins Sidney Kimmel Comprehensive Cancer Center,5Hôpital Européen Georges Pompidou,6Roswell Park Cancer Institute,7Hospital Universitario,8University of Michigan,9Instituto Oncologico de Cordoba,10IUCT-O Institut Claudius Regaud,11Fox Chase Cancer Center,12Stanford Cancer Institute,13Fondazione Istituto Nazionale,14Vanderbilt University Medical Center,15Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center,16Dana-Farber Cancer Institute/Brigham and Women’s Hospital,17Bristol-Myers Squibb,18Memorial Sloan Kettering Cancer Center,19Swansea University

Abstract

Background

CheckMate 025 (≥14-month follow-up) demonstrated superior OS with nivolumab versus everolimus (25.0 vs 19.6 months) and a higher ORR (25% vs 5%) in previously treated patients with aRCC. We report an exploratory analysis of 3-yr efficacy and safety.

Method

Adults with clear-cell aRCC that progressed after 1-2 antiangiogenic therapies were randomized (1:1) to nivolumab 3 mg/kg IV every 2 weeks or everolimus 10 mg orally once daily until progression/unacceptable toxicity. Endpoints: primary, OS; secondary: ORR, PFS, AEs.

Results

Overall, 410 (nivolumab) and 411 (everolimus) patients were randomized (27 and 3 continue to receive treatment as randomized). With median follow-up of 24 months (nivolumab) and 19 months (everolimus), median OS was 25.8 versus 19.7 months, respectively (hazard ratio [HR], 0.74; P=0.0005); 2-year OS rates were 52% and 42% and 3-year OS rates were 39% and 30%. Investigator-assessed unconfirmed ORR was consistent with the primary analysis: 26% (nivolumab) and 5% (everolimus). Median duration of response was 12.3 months for nivolumab responders and 12.0 months for everolimus responders. Ongoing response was noted in 18% (17/93) of nivolumab responders and 6% (1/17) of everolimus responders. Median (95% confidence interval) PFS was 4.2 months (3.7-5.4) with nivolumab and 4.5 months (3.8-5.5) with everolimus (HR, 0.85; P=0.0371). Incidence and type of treatment-related AEs were consistent with the primary analysis and remained lower with nivolumab (80%; grade 3-4, 21%) versus everolimus (89%; grade 3-4, 37%). Most treatment-related select AEs with nivolumab resolved (75%-100%, by AE category), except for endocrine AEs (38%), which required permanent hormone replacement. Quality-of-life improvement with nivolumab was consistent with earlier analyses.

Conclusion

In this 3-year update, nivolumab continues to demonstrate durable responses and survival benefit versus everolimus in previously treated patients with aRCC. The safety profile is favorable, consistent with the primary analysis, and most AEs were manageable with the majority having resolved.