742 IO combinations meta-analysis in 1L mRCC

<h3>Background</h3> The past decade has seen multiple treatment advances in Metastatic Renal Cell Carcinoma (mRCC). Despite the approvals in immuno-oncology (IO)-based combination therapy, the standard of care first-line (1L) therapy for mRCC remains an active debate. Here, we compare the efficacy of IO combinations in 1L mRCC, including the latest data releases in 2024. <h3>Methods</h3> A systematic review in LARVOL CLIN - a comprehensive oncology database of 100,000 trials, 95k+ Kaplan-Meier (KM) curves, and 15k+ Hazard Ratios (HRs) - was conducted to identify trials comparing IO combinations to sunitinib, which has long been considered the standard of care (SOC) for 1L mRCC. A meta-analysis was performed on phase 3 trials using KM curve data and HRs extracted from the latest publications. <h3>Results</h3> 5 trials - Checkmate 214, Checkmate 9ER, KEYNOTE 426, CLEAR and JAVELIN Renal 101- were identified for 1L mRCC with mature survival data on IO combinations vs sunitinib (table 1), all of which evaluated PFS as the primary outcome. Each trial includes a distinct combination of two IOs or an IO plus a tyrosine kinase inhibitor (TKI). The CLEAR trial, which analyzes the combination of pembrolizumab plus lenvatinib, shows the most significantly improved survival as measured by median PFS (figure 1). OS improvement was also significant for trials with this coprimary outcome. However, the final analysis of JAVELIN Renal 101 did not show a significant OS improvement from nivolumab with axitinib vs sunitinib, despite initial data releases (figure 2). <h3>Conclusions</h3> The FDA granted its first approval for an IO combination in the context of 1L mRCC based on Checkmate214. This trial paved the way for further research into various IO combinations, including those examined here. The dual IO combinations and IO plus TKI combinations evaluated demonstrated significantly better outcomes than sunitinib, suggesting a potential shift from considering sunitinib as the standard of care for 1L mRCC. However, according to the most recent JAVELIN Renal 101 updates, the OS advantage of avelumab with axitinib failed to be statistically significant compared to other IO combinations. <h3>Trial Registration</h3> NCT02231749 NCT03141177 NCT02853331 NCT02811861 NCT02684006.