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

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. 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. 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%, <i>p</i> = 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 (<i>p</i> &lt; 0.01). Steroid use also improved OS (<i>p</i> = 0.04). 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. Advanced kidney cancer is often treated with combination therapies that include immune checkpoint inhibitors (ICIs). These treatments help the immune system attack cancer cells but can also cause side effects, known as adverse events (AEs). This study examined how common these side effects are and whether they affect patient outcomes. We analyzed data from patients treated with three different ICI-based therapies at four Italian oncology centers. We found that most patients experienced AEs, with some side effects occurring more often depending on the type of treatment. Severe side effects were more frequent in patients receiving a combination of ICIs and another type of drug called tyrosine kinase inhibitors (TKIs). Importantly, we discovered that experiencing AEs did not shorten survival. In fact, some treatment adjustments, such as reducing the dose of TKIs or using steroids to manage side effects, were linked to better survival. These findings highlight the importance of managing treatment-related toxicities effectively. For patients, this means that while side effects are common with these treatments, they do not necessarily mean worse outcomes. With careful monitoring and adjustments, doctors can help patients continue therapy safely, potentially improving their chances of better long-term results.