Treatment-free survival (TFS) after discontinuation of first-line nivolumab (NIVO) plus ipilimumab (IPI) or sunitinib (SUN) in intention-to-treat (ITT) and IMDC favorable-risk patients (pts) with advanced renal cell carcinoma (aRCC) from CheckMate 214.

564 Background: TFS characterizes the antitumor activity of immuno-oncology agents after treatment discontinuation. In CheckMate 214, pts with IMDC intermediate/poor-risk aRCC who discontinued first-line NIVO+IPI experienced significantly longer TFS than those who discontinued SUN (McDermott et al, ESMO 2018). Here, we continue the analysis of TFS from CheckMate 214 in ITT and IMDC favorable-risk pts. Methods: Pts with previously untreated, predominantly clear cell aRCC were randomized 1:1 to intravenous NIVO 3 mg/kg + IPI 1 mg/kg every 3 weeks for 4 doses followed by NIVO 3 mg/kg every 2 weeks, or oral SUN 50 mg daily for 4 weeks on, 2 weeks off (6-week cycles). TFS was defined as the time from protocol therapy cessation to the start of subsequent systemic anticancer therapy or death, whichever occurred first. TFS in pts who discontinued NIVO+IPI or SUN was compared using Kaplan–Meier methods and log-rank tests. This analysis was conducted for all ITT (NIVO+IPI, 550; SUN, 546) and IMDC favorable-risk (NIVO+IPI, 125; SUN, 124) pts in CheckMate 214. Results: Among 463 NIVO+IPI and 477 SUN ITT pts who discontinued protocol therapy, the median TFS was 3.0 months with NIVO+IPI vs 1.3 months with SUN (HR [95% CI]; 0.54 [0.46–0.62]; P<0.0001); the TFS rates 2 years post-discontinuation were 21% vs 7%, respectively. In IMDC favorable-risk pts, 111 and 94 pts discontinued from NIVO+IPI and SUN, respectively. TFS in IMDC favorable-risk pts was also significantly longer with NIVO+IPI vs SUN (median, 6.3 vs 1.1 months; HR [95% CI]; 0.47 [0.34–0.65]; P<0.0001). The TFS rates 2 years post-discontinuation in favorable-risk pts were 29% for NIVO+IPI vs 13% for SUN. Conclusions: Similar to the TFS benefit seen in intermediate/poor-risk pts with aRCC, first-line therapy with NIVO+IPI resulted in reduced need for second-line therapy in ITT and IMDC favorable-risk pts compared with SUN. The durable TFS benefit across risk groups despite discontinuation of therapy provides further evidence of the encouraging benefit-risk profile of NIVO+IPI over SUN in pts with previously untreated aRCC. Clinical trial information: NCT02231749.

Duke Scholars

Author Michael Roger Harrison Medicine, Medical Oncology