Incidence and impact of immune combination therapies adverse events in advanced renal cell carcinoma patients

Background: Immune (IO)-combination therapies have revolutionized the treatment of advanced renal cell carcinoma (aRCC) but are more frequently associated with adverse events (AEs) compared to tyrosine kinase inhibitors (TKI) alone. This retrospective study aimed to evaluate the incidence and prognostic significance of AEs in patients receiving combination therapies. Methods: We included patients treated with nivolumab/ipilimumab (NI), nivolumab/cabozantinib (NC), or pembrolizumab/axitinib (PA) at four Italian oncology centers between November 2023 and June 2024. The impact of AEs on progression-free survival (PFS), overall survival (OS), overall response, and disease control rate were analyzed using descriptive statistics, Kaplan-Meier method, and Cox regression. Results: AEs occurred in 78.8% of NI, 87.9% of NC, and 92.3% of PA patients. Grade 3-4 AEs were more common in IO-TKI vs. IO-IO combinations (32.9% vs. 15.1%, p = 0.05). Pruritus and pulmonary events were more frequent with IO-IO, while hypertension and mucositis were more common with IO-TKI. High-grade AEs did not impact PFS or OS, but TKI reduction due to AEs was associated with longer OS (p < 0.01). Steroid use also improved OS (p = 0.04). Conclusion: AEs are common in ICI-based therapies for RCC. While they do not negatively affect survival, their management, especially through dose reductions or steroids, may improve outcomes.