First-Line Immune Checkpoint Inhibitor-Based Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review

Abstract

Background: Immune checkpoint inhibitors (CPIs) have come to the forefront as a major component of the management of metastatic renal cell carcinoma (mRCC). Over a short period of time, several studies have shown benefit in using these agents in the first-line setting. Objective: In this systematic review, the available evidence regarding the use of CPI-based regimens in previously untreated mRCC was reviewed. Methods: A systematic search for phase II and III studies was conducted of the PubMed and Embase databases as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The search retrieved abstracts to February 1, 2020. Data was compiled and summarized in narrative and tabular formats. Results: Fifty-five abstracts from 11 clinical trials were included, including four phase III clinical trials and seven phase II trials. The most recent phase III data demonstrates overall survival (OS) benefit for ipilimumab plus nivolumab (for intermediate and poor risk patients) and pembrolizumab plus axitinib combination regimens over sunitinib. Two other regimens (avelumab plus axitinib and atezolizumab plus bevacizumab) have shown benefits in progression free survival, but not in OS to date. Toxicity data shows varying patterns of adverse events between the four treatments. Phase II data indicate CPI has activity as a single agent, and in patients with non-clear cell subtypes of RCC. Conclusions: CPI-based regimens improve outcomes in virtually all subgroups of mRCC patients when used as front-line therapy. This is certain to change the landscape of mRCC treatment.