Nationwide Real-World Outcomes of Trial Eligible and Trial Ineligible Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab

INTRODUCTION: Clinical trials have demonstrated efficacy and safety of immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma (mRCC). However, patients who do not meet trial eligibility criteria constitute a large proportion of the real-world population, and their outcomes remain poorly described. PATIENTS AND METHODS: This nationwide, retrospective cohort study included all Danish patients with mRCC who initiated nivolumab plus ipilimumab (NIVO/IPI) by May 5, 2022. Clinical data were obtained from electronic patient records. Outcomes included median progression-free survival (mPFS), median overall survival (mOS), and objective response rate (ORR), assessed by treating physicians. Patients were classified as trial-eligible or ineligible according to CheckMate 214 (CM214) key criteria. Survival was estimated using Kaplan-Meier methods, and subgroups were explored. RESULTS: A total of 464 patients were included, with a median follow-up of 33 months. In the total cohort, mPFS was 9 months, mOS 41 months, and ORR 43%, including 13% complete responses. Among 282 trial-eligible patients, outcomes were comparable to CM214 with mPFS 12 months and mOS 49 month, while 182 ineligible patients had inferior outcomes, with mPFS 6 months and mOS 26 months (both P < .001). The presence of brain metastases did not adversely affect OS, while patients with autoimmune disease demonstrated unexpectedly favorable outcomes. Severe treatment-related toxicity (≥ grade 3) occurred in 44% in the total cohort, comparable to CM214. CONCLUSION: This is the first nationwide real-world study evaluating NIVO/IPI outcomes in unselected mRCC. Trial-eligible patients achieved survival outcomes comparable to clinical trial results. Although ineligible patients derived less benefit, they still experienced meaningful clinical outcomes. These findings provide benchmark data for treatment of real-world mRCC populations in routine clinical practice.