Outcomes of Nivolumab-Plus-Ipilimumab in Metastatic Renal Cell Carcinoma: Second Interim Analysis of the J-ENCORE Study.

[OBJECTIVES] J-ENCORE is a multicenter prospective observational study in Japan involving advanced or metastatic renal cell carcinoma patients receiving nivolumab-plus-ipilimumab (NIVO+IPI) as first-line treatment. The minimum 1-year observation revealed the efficacy and safety of NIVO+IPI comparable to those in CheckMate 214, and evaluated patient characteristics across subgroups for response and early progression. This minimum 2-year observation focuses on the post-treatment status after NIVO+IPI discontinuation.

[METHODS] The objective response rate (ORR), response duration, progression-free survival (PFS), overall survival (OS), treatment-related adverse events (TRAEs), treatment-free status, and second-line treatment were evaluated.

[RESULTS] The study included 274 patients (median age, 68 years; 24.8% aged ≥ 75 years; 15.7% had an Eastern Cooperative Oncology Group performance status ≥ 2; 58.0%, intermediate risk; 42.0%, poor risk) from 37 sites, with a median follow-up of 35.4 (range, 24.4-47.0) months. The ORR was 37.6%, with a median real-world duration of response at 17.1 months; 30.2% had real-world PFS ≥ 24 months, and the OS rate at 24 months was 67.2%. TRAEs of any grade, grade 3/4, and grade 5 occurred in 77.4%, 42.7%, and 1.1% of patients, respectively. Furthermore, 11.1% experienced late-onset TRAEs 28-100 days after discontinuation. For patients discontinuing NIVO+IPI due to adverse events, median treatment-free survival was 7.4 months; 34.9% had a treatment-free interval ≥ 12 months. Second-line treatment ORR was 22.0%, with cabozantinib as the most common choice.

[CONCLUSIONS] We determined the long-term real-world effectiveness and safety of NIVO+IPI, providing beneficial information on post-treatment status.

[TRIAL REGISTRATION] UMIN Clinical Trials Registry number: UMIN000036772; ClinicalTrials.gov identifier: NCT04043975.