Effectiveness and safety of first-line nivolumab-ipilimumab in metastatic renal cell carcinoma.

Abstract

Background/AimThe combination of nivolumab and ipilimumab is the standard first-line treatment for patients with metastatic renal cell carcinoma (mRCC) of intermediate or poor IMDC risk. However, real-world data in unselected populations remain limited. We aimed to evaluate the effectiveness and safety of nivolumab-ipilimumab in a real-world cohort and to describe subsequent therapies after progression.Patients and MethodsWe conducted a retrospective, observational, real-world study at a Spanish tertiary hospital. All adults with intermediate- or poor-risk mRCC who received first-line nivolumab-ipilimumab between January 2018 and June 2025 were included. Overall survival (OS), progression-free survival (PFS), second progression-free survival (PFS2), overall response rate (ORR), disease control rate (DCR), duration of response (DOR) and immune-related adverse events (irAEs) were evaluated. Survival was estimated using the Kaplan-Meier method. Exploratory subgroup analyses were performed according to Eastern Cooperative Oncology Group performance status (ECOG PS), histology, metastatic sites and presence of irAEs.ResultsForty-three patients were included; median age was 64 years and 83.7% were male. Most patients had ECOG PS 0-1 (79%), clear-cell histology (86%) and 28% had sarcomatoid features. Brain metastases were present in 14%. After a median follow-up of 32.2 months, median OS was 18.4 months; the 12 and 36-month OS rates were 59.0% and 44.0%, respectively. Median PFS was 5.1 months; the 12 and 36-month PFS rates were 29.4% and 25.7%, respectively. ORR was 27.9% (4.7% complete responses, 23.2% partial responses) and DCR was 46.5%. Among responders, median DOR was not reached; 81.8% and 68.2% remained free of progression at 12 and 36 months, respectively. Any-grade irAEs occurred in 51.2% of patients, grade ≥3 irAEs in 34.8%, and 16.3% discontinued treatment due to toxicity. ECOG PS ≥2 was associated with significantly worse OS (HR 8.59; p = 0.0029), whereas the occurrence of irAEs was associated with improved OS (HR 0.14; p = 0.001).ConclusionIn this real-world cohort of intermediate/poor-risk mRCC, nivolumab-ipilimumab showed lower median OS and PFS than in pivotal trials and some real-world series, likely reflecting poorer baseline prognostic features. Nevertheless, a clinically relevant subgroup of long responders achieved durable benefit, and the safety profile was consistent with previous reports. Nivolumab-ipilimumab remains an effective first-line option in real-world practice, particularly in patients achieving early disease control.