A Minimum 3‐Year Follow‐Up of Nivolumab‐Plus‐Ipilimumab in Japanese Patients With Advanced or Metastatic Renal Cell Carcinoma: A Final Analysis of the J‐ ENCORE Study

OBJECTIVES: The J-ENCORE study is a Japanese multicenter, prospective observational study involving patients with advanced or metastatic renal cell carcinoma treated with nivolumab-plus-ipilimumab combination as first-line treatment. Interim 1- and 2-year reports demonstrated efficacy and safety comparable to those of the CheckMate 214 trial, with sustained effects after nivolumab-plus-ipilimumab discontinuation, and explored outcome-associated factors. This final analysis of a minimum 3-year observation summarized long-term outcomes, including real-world second progression-free survival and overall survival, and explored outcome-associated factors. METHODS: Real-world objective response rate, response duration, real-world progression-free survival, overall survival, treatment-related adverse events, and real-world second progression-free survival were evaluated. Outcome-associated factors were explored. RESULTS: The study included 274 patients (68.2% aged ≥ 65 years; 42.0%, poor risk) from 37 sites, with a median follow-up of 47.4 (range, 36.5-59.0) months. Real-world objective response rate was 38.4%, with 30.5% maintaining ≥ 36 months response duration. Median real-world progression-free survival and second progression-free survival were 9.7 and 30.1 months, respectively, and 60.2% of patients survived for ≥ 36 months. Treatment-related adverse events of any grade, grade 3/4, and grade 5 occurred in 78.5%, 43.1%, and 1.1% of patients, respectively. No new treatment-related adverse events or increased frequencies were reported since the previous interim analyses. Multivariable analyses identified associations between overall survival and age, lactate dehydrogenase levels, and C-reactive protein levels, with favorable prognosis in patients with none or one of these factors. CONCLUSIONS: We demonstrated long-term real-world outcomes of nivolumab-plus-ipilimumab. Our findings support prescriptions of nivolumab-plus-ipilimumab in real-world clinical practice. TRAIL REGISTRATION: UMIN Clinical Trials Registry: UMIN000036772 and ClinicalTrials.gov: NCT04043975.