Two-Year Efficacy and Safety Update: Phase III CheckMate 025 Study of Nivolumab vs Everolimus in Patients With Advanced Renal Cell Carcinoma (aRCC)


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Elizabeth R. Plimack1,Robert J. Motzer2,Bernard Escudier3,Padmanee Sharma4,David F. McDermott5,Saby George6,Hans J. Hammers7,Michael Carducci7,Scott S. Tykodi8,Jeffrey A. Sosman9,Toni K. Choueiri10,Frede Donskov11,Howard Gurney12,Thomas C. Gauler13,Takeshi Ueda14,Huanyu Zhao15,Elmer Berghorn15,John Wagstaff16
1Fox Chase Cancer Center,2Memorial Sloan Kettering Cancer Center,3Gustave Roussy,4MD Anderson Cancer Center, University of Texas,5Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center,6Roswell Park Cancer Institute,7Johns Hopkins Sidney Kimmel Comprehensive Cancer Center,8University of Washington and Fred Hutchinson Cancer Research Center,9Vanderbilt University Medical Center,10Dana-Farber Cancer Institute/Brigham and Women’s Hospital,11Aarhus University Hospital,12Westmead Hospital and Macquarie University,13University Hospital Essen of University of Duisburg-Essen,14Chiba Cancer Center,15Bristol-Myers Squibb,16South West Wales Cancer Institute and Swansea University College of Medicine

Abstract

Background

The primary analysis of CheckMate 025, based on 14 months’ minimum follow-up, demonstrated superior overall survival (OS) with nivolumab vs everolimus (25.0 vs 19.6 months) and a higher objective response rate (ORR; 25% vs 5%) in previously treated patients with aRCC (N Engl J Med 2015;373:1803-13). Here, we report 2-year follow-up of efficacy and safety.

Method

Adults with clear-cell aRCC, progressed after 1-2 prior anti-angiogenic therapies, were randomized (1:1) to nivolumab 3 mg/kg IV every 2 weeks or everolimus 10 mg orally once daily until progression or unacceptable toxicity. Primary endpoint: OS. Key secondary endpoints: ORR, progression-free survival, and incidence of adverse events (AEs).

Results

Minimum follow-up was 26 months. Median OS was 26.0 months with nivolumab and 19.7 months with everolimus (hazard ratio = 0.73; P=0.0006); 1- and 2-year OS rates were 76% and 52% with nivolumab, and 67% and 42% with everolimus, respectively. ORR remained consistent with the primary analysis, at 26% and 5%. Median duration of response was 12.0 months for the 105 nivolumab responders and 12.0 months for the 22 everolimus responders. Ongoing response was noted in 29% (nivolumab) and 14% (everolimus) of patients. Incidence and type of treatment-related AEs were consistent with the primary analysis and remained lower with nivolumab (79%; grade 3-4, 20%) vs everolimus (88%; grade 3-4, 37%). The majority of treatment-related select AEs with nivolumab resolved (63%-89%, depending on AE category), with the exception of endocrine AEs (37%). Analyses of potential prognostic factors for OS and characteristics of patients based on response status at 2 years will be presented.

Conclusion

In this 2-year update, nivolumab continues to demonstrate durable responses and a survival benefit over everolimus in previously treated patients with aRCC. The safety profile is consistent with the primary analysis, and most patients’ AEs resolved.

Originally presented at ESMO, 7-11 October 2016, Copenhagen, Denmark