Real-world outcomes of nivolumab plus ipilimumab versus immune checkpoint inhibitor and tyrosine kinase inhibitor combinations as first-line treatment for metastatic clear cell renal cell carcinoma.

e16510 Background: The management of metastatic clear cell renal cell carcinoma (mccRCC) has evolved significantly with the introduction of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). However, limited real-world data exist comparing the efficacy of nivolumab plus ipilimumab (N/I) with ICI plus TKI (IO/TKI) combinations. This study evaluates progression-free survival (PFS), overall survival (OS), and other efficacy parameters for these regimens in patients with mccRCC treated at tertiary care centers in Saudi Arabia. Methods: This retrospective, multicenter study included patients with mccRCC treated with first-line N/I or IO/TKI between 2018 and 2022. Eligible patients had confirmed clear cell histology, were treatment-naïve, and received first-line ICIs. Patient demographics, IMDC risk groups, treatment regimens, and efficacy outcomes were analyzed. PFS and OS were calculated using Kaplan-Meier estimates. Univariate and multivariate analyses were performed to identify factors affecting outcomes. Results: A total of 99 patients were included, with 33 receiving N/I and 66 receiving IO/TKI. Patients in the IO/TKI group had a higher proportion of Furhman grade 3–4 tumors (47% vs. 30%) and prior nephrectomy (53% vs. 39%), while more patients in the N/I group presented with N1 disease (33% vs. 17%) and de novo metastatic disease (82% vs. 68%). Median PFS for the overall cohort was 16 months (95% CI: 12.6-19.4); PFS was significantly longer in the IO/TKI group (21.36 months, 95% CI: 13.08–29.63) compared to the N/I group (10.49 months, 95% CI: 1.60–19.29; p = 0.03). OS was not reached in either group, with 3-year OS rates of 57% (95% CI: 34–74%) for N/I and 67% (95% CI: 19–77%) for IO/TKI (p = 0.2). Multivariate analysis showed that IO/TKI use (p = 0.03) and lymphocyte-to-platelet (L/P) ratio > 6.14 (p = 0.003) were independently associated with improved PFS, while pure clear cell histology (p = 0.04), L/P ratio > 6.14 (p = 0.006), and absence of bone metastasis (p = 0.02) were associated with improved OS. Conclusions: In this real-world analysis, IO/TKI combinations demonstrated significantly longer PFS compared to N/I, with comparable OS outcomes. The findings highlight the importance of individualized treatment selection based on patient characteristics, including disease presentation, risk stratification, and tumor features.