Efficacy of Immune Checkpoint Inhibitors vs Tyrosine Kinase Inhibitors/Everolimus in Adjuvant Renal Cell Carcinoma: In-direct Comparison of Disease-Free Survival

Abstract

Background: The proven efficacy of mTOR inhibitors (mTORI), tyrosine kinase inhibitors (TKI) or immune checkpoint inhibitors (ICI) therapies in metastatic renal cell carcinoma (RCC), suggested that these agents should be investigated as adjuvant therapy with the aim of eliminating any residual undetectable microscopic disease after curative resection. Our study aimed to compare the efficacy of these treatments through the application of an innovative method that reconstructs individual patient data. Methods: Nine phase III studies describing different treatment options for adjuvant RCC were selected. Individual patient data were reconstructed from Kaplan–Meier (KM) curves through the “IPDfromKM method”. Disease-free survival (DFS) were compared among combination treatments and control arm (placebo). Results were summarized as multi-treatment KM curves. Standard statistical testing was used, including hazard ratio and likelihood ratio tests for heterogeneity. Results: In the overall population, this study showed that two ICIs (pembrolizumab and nivolumab plus ipilimumab) and one TKI (sunitinib) showed superiority over placebo, whereas both TKI and mTORI did not. As we assessed DFS as the primary endpoint for the adjuvant comparison, the overall survival benefit remains unknown.. Conclusion: This novel approach to investigating survival has allowed us to conduct all of the indirect head-to-head comparisons between these agents in a context where no "real" comparative trials have been conducted.