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

ABSTRACT 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