Real-world outcomes of dual checkpoint blockade versus PD-1/VEGF inhibitor combination as first-line therapy in metastatic renal cell carcinoma.

e16550 Background: Immune-based combinations have upstaged traditional treatment regimens by becoming the first-line therapy for advanced/metastatic renal cell carcinoma. Nivolumab-ipilimumab and PD-1/VEGF inhibitor combinations each have distinct benefits; however, comparative data are limited due to a lack of large-scale clinical trials. This study aims to evaluate the outcomes of the two treatment regimens to refine therapy choices. Methods: We set out to perform a multicenter retrospective cohort study to compare Nivolumab-Ipilimumab with Pembrolizumab-Lenvatinib and Nivolumab-Cabozantinib as first-line therapy in Metastatic/Advanced Renal Cell Carcinoma. We utilized real-world data from the TriNetX database spanning between January 2011 and December 2024. Eligible patients were identified using ICD-10-CM codes related to metastatic RCC and Advanced RCC. Propensity Score matching was used to characterize and balance the cohorts based on age, gender, and ethnicity. We measured the real-world overall and progression-free survival between the compared cohorts using the log-rank test, Kaplan-Meier survival curves, and Cox proportional hazard ratios. Results: Using TriNetX data, we performed two propensity-matched comparative arms. Arm 1 compares the outcomes between the cohorts Nivolumab-Ipilimumab and Pembrolizumab-Lenvatinib, with Arm 2 comparing cohorts Nivolumab-Ipilimumab and Nivolumab-Cabozantinib. After matching, Arm 1 included 965 patients, which showed no significant difference in both overall survival (1,224 vs 1,126 days; hazard ratio 0.919; 95% CI 0.79,1.068, p-value 0.66) and progression-free survival (85 vs 126 days; hazard ratio 1.23; 95% CI 0.932,1.623, p-value 0.927). Arm 2 included 2,498 patients and showed a statistically significant difference in overall survival (1,117 vs 786 days; hazard ratio 0.78; 95% CI 0.719,0.845; p-value < 0.0001) but no significant progression-free survival (100 vs 167 days; hazard ratio 1.18; 95% CI 0.982,1.433; p-value 0.089). Thus, demonstrating a significant overall survival in patients who received Nivolumab-Cabozantinib compared to Nivolumab-Ipilimumab. Conclusions: The treatment landscape of Metastatic/Advanced Renal Cell Carcinoma has evolved significantly with the advent of dual checkpoint inhibitors and PD-1/VEGF inhibitor combinations. In this multicenter retrospective cohort study, Pembrolizumab-Lenvatinib showed no significant change in patients’ overall survival and progression-free survival compared to the Nivolumab-Ipilimumab combination. In contrast, Nivolumab-Cabozantinib had superior overall survival compared to Nivolumab-Ipilimumab, though there was no significant difference in progression-free survival. These findings, projecting from real-world data, would aid clinicians in making effective treatment decisions.