Treatment-related adverse events of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors in clinical trials: a meta-analysis.

Aim: PD-1/PD-L1 inhibitors in combination with CTLA-4 inhibitors are being tested in a number of ongoing clinical trials. As a result, it is critical to fully comprehend the toxicity characteristics of adverse events in combination therapy. This study aims to extensively compare the incidences and ORs of treatment-related adverse events between two combination strategies.

Methods: The eligible articles were searched from PubMed, EMBASE and Cochrane databases for studies published between 1 January 2010 and 1 May 2021, investigating PD-1/PD-L1 inhibitors plus CTLA-4 inhibitor-based combined clinical therapies. The mean incidences and pooled ORs of all-grade and grade 3 or higher adverse events were calculated by random-effects model using Stata 12.1. Heterogeneity between studies was assessed with I² statistics and Chi square-based Q statistic. The overall risk of bias was assessed by Review Manager 5.3.

Results: A total of 26 eligible studies of 3607 patients were selected; 2852 patients developed at least one all-grade adverse event. PD-L1 inhibitors plus CTLA-4 inhibitors regimen (incidence 0.67, 95% CI: 0.57-0.77) had marked advantage over PD-1 inhibitors plus CTLA-4 inhibitors regimen (incidence 0.89, 95% CI: 0.86-0.93).

Conclusion: PD-L1 inhibitors plus CTLA-4 inhibitors shows better safety in treatment-related adverse events than PD-1 inhibitors plus CTLA-4 inhibitors.