Nivolumab plus ipilimumab (NIVO+IPI) vs sunitinib (SUN) for first-line treatment of advanced renal cell carcinoma (aRCC): Long-term follow-up data from the phase 3 CheckMate 214 trial

Background: First-line NIVO+IPI has provided substantial long-term survival benefits over SUN in patients (pts) with aRCC in CheckMate 214. We report survival, response per independent radiology review committee (IRRC) and safety after 6 y minimum (80 mo median) followup in all randomized pts, by IMDC risk and in pts with overall survival (OS) $ 6 y (long-term survivors; LTS). Longer follow-up data (minimum, 7.5 y) will be presented. Methods: Pts with clear cell aRCC were randomized 1:1 to NIVO 3 mg/kg + IPI 1 mg/kg Q3W34 then NIVO 3 mg/kg Q2W vs SUN 50 mg QD for 4 wk on, 2 wk off. Endpoints: OS, progression-free survival (PFS) and objective response rate (ORR; both per IRRC using RECIST v1.1) in IMDC intermediate/poor risk (IP; primary), intent-to-treat (ITT; secondary) and favorable risk (FAV; exploratory) pts. Exploratory outcomes in LTS pts were assessed post hoc. Results: OS with NIVO+IPI vs SUN remained superior in ITT (HR 0.72) and IP (HR 0.68) pts; OS benefits were similar between arms in FAV pts (HR 0.87; Table). Median PFS was consistent with previous reports. ORR per IRRC was higher with NIVO+IPI vs SUN, with more ongoing responses in ITT (60% vs 50%) and IP (60% vs 50%) pts. In FAV pts, ORR was lower with NIVO+IPI vs SUN, yet more responses were ongoing (59% vs 52%, respectively). Median duration of response (DOR) was longer and complete response (CR) rate was higher with NIVO+IPI vs SUN regardless of IMDC risk. Incidence of any and grade 3-4 treatment-related adverse events remained largely unchanged. No new drug-related deaths occurred in either arm since the previous database lock. In the LTS subgroup (NIVO+IPI, n = 208; SUN, n = 151), ORR was higher (66% vs 53%), more pts had a CR (27% vs 9%) and fewer progressed (4% vs 11%) with NIVO+IPI vs SUN. Median DOR was longer with NIVO+IPI (n = 137) vs SUN (n = 80) among LTS with confirmed response (76 vs 40 mo). Updated survival, response and safety data with 7.5 y minimum follow-up, along with additional subgroup analyses, will be presented. Conclusions: NIVO+IPI demonstrated long-term survival and more durable response benefits vs SUN in ITT and IP pts. CR rates were higher and median DOR was longer with NIVO+IPI vs SUN regardless of IMDC risk group, and in LTS pts. No new safety signals emerged. Clinical trial information: NCT02231749. Research Sponsor: Bristol Myers Squibb.