Treatment-free interval (TFI) following discontinuation of first-line nivolumab plus ipilimumab (N+I) or sunitinib (S) in patients (Pts) with advanced renal cell carcinoma (aRCC): CheckMate 214 analysis

Abstract

Background: Pts with metastatic melanoma who discontinue N+I may experience sustained clinical benefit and a delayed need for subsequent therapy. In this analysis, TFI was retrospectively analyzed using data from the phase 3 CheckMate 214 trial, in which N+I demonstrated superior efficacy vs S in pts with IMDC intermediate/poor (int/ poor)‐risk aRCC. Methods: In CheckMate 214, pts with previously untreated clear cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg every 3 weeks for 4 doses followed by N 3 mg/kg every 2 weeks, or S 50 mg daily orally for 4 weeks (6‐week cycles). TFI was defined as the time from last dose of N+I or S to the start of subsequent systemic therapy or death. All randomized pts with IMDC int/poor‐risk aRCC (N+I, 425; S, 422) were analyzed. Kaplan‐Meier curves and log‐rank tests were used to compare TFI between N+I and S. Results: With median overall survival follow‐up of 25.2 months, pts in the N+I arm had significantly longer time from randomization to subsequent systemic therapy or death than pts in the S arm (median, 15.4 vs 8.5 months; P<0.0001); 2 years after randomization, 42% vs 19% of pts were alive and not requiring subsequent therapy. Overall, 320 (75%) N+I pts and 359 (85%) S pts discontinued treatment, most commonly due to disease progression (N+I, 42%; S, 58%) or study drug‐related adverse events (N+I, 23%; S, 11%). In pts who discontinued, TFI was significantly longer with N+I than with S (P<0.0001); 18 months after discontinuation, 19% of N+I pts vs 4% of S pts remained treatment‐free. TFI was also significantly longer with N+I than with S, irrespective of best overall response on study (P<0.0001). 18 months after discontinuation, 48% of N+I pts vs 6% of S pts with complete/partial response were still free of subsequent treatment; at the same time point, 13% of N+I pts vs 4% of S pts with stable disease remained treatment‐free. Conclusions: The use of N+I was associated with a significant longer TFI beyond treatment discontinuation in pts with IMDC int/poor‐risk aRCC and irrespective of whether pts achieved response or disease control. TFI should be considered along with traditional efficacy measures when evaluating treatment options for aRCC.