Characterization of the benefit-risk profile of nivolumab + ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced renal cell carcinoma (aRCC; CheckMate 214).

Abstract

686 Background: The phase 3 CheckMate 214 study demonstrated superior efficacy for N+I v S in intermediate/poor-risk aRCC patients (pts), with manageable safety (Escudier, ESMO 2017). Here we report additional data to define benefit-risk. Methods: Pts with clear-cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg every 3 wk for 4 doses followed by N 3 mg/kg every 2 wk, or S 50 mg daily orally for 4 wk (6-wk cycles). Primary endpoints were efficacy parameters in intermediate/poor-risk pts. Secondary endpoints included adverse event (AE) incidence in all treated pts. Select AEs were defined as AEs pooled by organ category that may differ from AEs caused by non-immunotherapies, may require immunosuppression, and whose early recognition may mitigate severe toxicity. Results: 1096 pts were randomized (pts treated: N+I: n = 547; S: n = 535). N+I showed statistically significant OS benefit, significantly higher ORR, numerically longer PFS, and better symptom control v S. 79% of N+I pts received all 4 I doses. Drug-related grade 3-5 AEs occurred in 46% with N+I v 63% with S; drug-related AEs leading to discontinuation occurred in 22% v 12%. Drug-related select AEs resolved in 72%-92% of N+I pts, except endocrinopathies (43%; Table). An analysis of the relationship between safety and efficacy will be presented. Conclusions: Drug-related select AEs with N+I were manageable, with the vast majority resolving except endocrinopathies. These additional data further support the favorable benefit-risk profile of N+I v S in CheckMate 214. Clinical trial information: NCT02231749. [Table: see text]