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

Simple Summary: The proven efficacy of mTOR inhibitor (mTORI), tyrosine kinase inhibitor (TKI) or immune checkpoint inhibitor (ICI) therapies in metastatic renal cell carcinoma (RCC) suggests that these agents should be investigated as adjuvant therapy with the aim of eliminating undetectable microscopic residual disease after curative resection. Our study aimed to compare the efficacy of these treatments using an innovative method that reconstructs individual patient data from Kaplan–Meier (KM) curves. Nine phase III trials describing different treatment options for adjuvant RCC were selected. Individual patient data were reconstructed from KM curves of disease-free survival (DFS) using the IPDfromKM method. DFS was then compared between the combination treatments and the control arm (placebo). The results were summarized as multi-treatment KM curves. Standard statistical tests were used, including the hazard ratio for superiority and the likelihood ratio test for heterogeneity. In the population of these nine trials, our study showed that two ICIs (nivolumab plus ipilimumab and pembrolizumab) and one TKI (sunitinib) were superior to the placebo, whereas the remaining TKIs and mTORIs were not. As we assessed DFS as the primary endpoint for the adjuvant comparison, the overall survival benefit remains unknown. This novel approach to studying survival has allowed us to make all of the indirect head-to-head comparisons between these agents in a context where no "real" comparative trials have been conducted. Background: The proven efficacy of mTOR inhibitors (mTORIs), tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) in metastatic renal cell carcinoma (RCC) suggests that these agents should be investigated as adjuvant therapy with the aim of eliminating undetectable microscopic residual disease after curative resection. The aim of our study was to compare the efficacy of these treatments using an innovative method of reconstructing individual patient data. Methods: Nine phase III trials describing adjuvant RCC treatments were selected. The IPDfromKM method was used to reconstruct individual patient data from Kaplan–Meier (KM) curves. The combination treatments were compared with the control arm (placebo) for disease-free survival (DFS). Multi-treatment KM curves were used to summarize the results. Standard statistical tests were performed. These included hazard ratio and likelihood ratio tests for heterogeneity. Results: In the overall population, the study showed that two ICIs (nivolumab plus ipilimumab and pembrolizumab) and one TKI (sunitinib) were superior to the placebo, whereas both TKIs and mTORIs were inferior. As we assessed DFS as the primary endpoint for the adjuvant comparison, the overall survival benefit remains unknown. Conclusions: This novel approach to investigating survival has allowed us to conduct all indirect head-to-head comparisons between these agents in a context where no "real" comparative trials have been conducted. [ABSTRACT FROM AUTHOR]