Real‐world efficacy and toxicity of ipilimumab and nivolumab as a first‐line treatment for advanced renal cell carcinoma according to IMDC risk criteria—A multi‐center retrospective analysis on behalf of the GUARDIANS group

Abstract Ipilimumab and nivolumab are recommended as first‐line therapy for patients with metastatic or advanced renal cell carcinoma (aRCC) and International Metastatic RCC Database Consortium (IMDC) intermediate or poor risk. We retrospectively evaluated efficacy and safety in a multi‐center real‐world cohort with 356 patients initiating ipilimumab and nivolumab from 17 centers in Germany and Switzerland. Median age was 64 years, most patients were male (69.1%) and had clear cell histology (74.1%). IMDC risk was intermediate in 61.8% and poor in 28.7%. About 37.1% of cases did not meet the inclusion criteria for the CheckMate 214 pivotal study (e.g., poor Eastern Cooperative Oncology Group Performance Status Scale ECOG status, comorbidities, brain metastases, and impaired renal function). After a median follow‐up of 17.5 months, complete response was seen in 8.7%, partial response in 28.7% of patients. Median progression‐free survival (PFS) was 8 (95% confidence interval CI 5.4–10.6) and median overall survival (OS) 39 months (95% CI 27.5–50.5). Subgroup analysis of patients with non‐clear cell histology showed a shorter PFS and OS. Other negative predictors were poor ECOG, fewer induction cycles, ineligibility to pivotal study, and hepatic metastases. Adverse events occurred in 76.4% of patients (35.4% ≥ grade 3). High‐dose corticosteroids were applied in 27.3% of cases. Cabozantinib was most frequently administered (63.4%) as subsequent therapy and showed superior OS and PFS compared to other second‐line options. Our data support ipilimumab and nivolumab as a first‐line treatment of aRCC with robust efficacy and safety. Patient selection was less restrictive in our clinical practice and may explain differences to CheckMate 214 trial.