# 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

## TL;DR

This study shows that combining ipilimumab and nivolumab is effective and safe for treating advanced kidney cancer in real-world patients, including those who are less healthy than those in clinical trials.

## Contribution

The study provides real-world evidence of ipilimumab and nivolumab's efficacy and safety in a broader, less-restricted patient population than clinical trials.

## Key findings

- The combination therapy showed a complete response in 8.7% and partial response in 28.7% of patients.
- Median overall survival was 39 months, with non-clear cell histology and poor ECOG status as negative predictors.
- Adverse events occurred in 76.4% of patients, but the treatment was generally well-tolerated in routine clinical practice.

## 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.

What's new?

The combination of ipilimumab and nivolumab as a first‐line treatment for advanced renal cell carcinoma has demonstrated durable response and tolerability in clinical trials. However, inclusion criteria for clinical studies are restrictive, and patients in the real‐world setting tend to have more comorbidities. Here, the authors retrospectively evaluated efficacy and safety in a multi‐center real‐world cohort of 356 patients initiating ipilimumab and nivolumab from 17 centers in Germany and Switzerland. The results support the efficacy and safety of ipilimumab and nivolumab combination in routine clinical practice, even with patients being frailer than those in the pivotal trial.