Immune-related adverse events with cancer clinical benefits: a systematic review and meta-analysis

Growing research have reported an association of the occurrence of immune-related adverse events (irAEs) and clinical benefits in patients with immune checkpoint inhibitors (ICIs) treatments, but the findings remain controversial. The aim of this study is to identify whether the incidence of irAEs and their subtypes undergoing ICIs treatment is associated with enhanced efficacy and survival benefits in all solid tumors. Cochrane Library, Embase, PubMed and Web of Science databases were searched from database inception and December 31, 2023. Two reviewers independently extracted data and reviewed the quality items using the Newcastle-Ottawa Scale criteria, and resolved any discrepancies by consensus discussion with third reviewer. We performed the systematic review and meta-analysis in compliance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology. The main outcomes were irAEs incidence, objective response rate (ORR), overall survival (OS) and progression-free survival (PFS). Subgroup and sensitivity analyses were performed. A total of 184 articles involving a total of 63,780 patients met the inclusion criteria. The pooled incidence of irAEs in this meta-analysis was 37.3% (95%CI: 34.4%-40.3%). The occurrence of irAEs was associated with increased ORR (RR, 2.32 95%CI, 2.02–2.67; I 2 = 80.1%; P < 0.001), and pooled ORRs in irAE+ versus irAE- patients were 39.4% (95%CI: 35.4%-43.5%) versus 16.2% (95%CI: 13.5%-19.4%). Besides, irAEs development presented better weighted average OS (20.03 months versus 10.83 months), and associated with longer OS (HR, 0.55 95%CI, 0.51–0.59; I 2 = 70.4%; P < 0.001). Similar finding in PFS, weighted average PFS in irAEs patients was 9.73 months versus 4.15 months in without irAEs patients, and irAEs occurrence improved PFS (HR, 0.58 95%CI, 0.53–0.63; I 2 = 50.8%; P < 0.001) compared with those who did not. The intimate association was observed between the development of irAEs and increased response rate and improved survival benefits in patients who treated with ICIs, and may have useful prognostic value in ICIs therapy.