To evaluate the efficacy and toxicity of ipilimumab and nivolumab in advanced clear cell renal cell carcinoma (ccRCC) and rare variant RCC, and assess the impact of immune-related adverse events (irAEs) and steroid use on survival.
This retrospective study included patients with advanced ccRCC and rare variant RCC treated with first-line ipilimumab and nivolumab at the Royal Marsden Hospital between 2016 and 2025. Survival, toxicity, and the impact of irAEs and steroid use were analyzed using landmark and time-dependent methods.
Among 154 patients, 35 had rare variant RCC and 18 had brain metastases (BM). Median follow-up was 20.3 months (ccRCC) and 24.2 months (rare variants). Median overall survival (OS) was 31.9 months (95% CI, 23.5-59.1) for ccRCC and 25.9 months (95% CI, 21.9-not estimable (NE)) for rare variants. Median progression-free survival (PFS) was 9.0 months (95% CI, 7.1-12.8) and 7.2 months (95% CI, 4.6-NE), respectively. Objective response rates (ORR) were 41.0% (ccRCC) and 38.2% (rare variants). In BM patients, median OS was 14.5 months (95% CI, 8.3-NE), PFS 6.2 months (95% CI, 3.3-NE), and ORR 27.8%. Grade 3-4 irAEs occurred in 28.4% and were associated with longer OS at 6-week landmark (NR vs. 23.1 months, P = .033). Prednisone ≥ 40 mg was associated with improved OS (61.2 vs. 22.3 months, P = .021), confirmed on multivariable analysis. Limitations include small sample size and retrospective design.
Ipilimumab and nivolumab demonstrated real-world efficacy in both ccRCC and rare variant RCC. Grade 3-4 irAEs and the use of high-dose steroids for their management were associated with improved OS.
Clinical genitourinary cancer. 2025 Nov 15 [Epub ahead of print]
Tobias Peres, James Larkin
Division of Medical Oncology, The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom. Electronic address: ., Division of Medical Oncology, The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41349226