CheckMate 025 (≥14-month follow-up) demonstrated superior overall survival (OS) with nivolumab versus everolimus (25.0 vs 19.6 months) and a higher objective response rate (ORR; 25% vs 5%) in previously treated patients with aRCC (NEJM 2015). Here we report an exploratory analysis of 3-yr efficacy and safety.

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 or unacceptable toxicity. Endpoints: primary, OS; key secondary: ORR, progression-free survival (PFS), adverse events (AEs).

Overall, 410 patients and 411 patients were randomized to nivolumab and everolimus, respectively (27 and 3 continue to receive treatment as randomized). With median follow-up of 24 months with nivolumab and 19 months with everolimus, median OS was 25.8 months and 19.7 months, respectively (hazard ratio [HR], 0.74; P=0.0005), with 2-year OS rates of 52% and 42% and 3-year OS rates of 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.

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