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

Abstract

Background/Aim

The 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 Methods

We 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.

Results

Forty-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).

Conclusion

In 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.