Cutaneous Adverse Events and Cancer Survival Prognosis With Immune Checkpoint Inhibitor Treatment

Importance: Growing research suggests that the prevalence of cutaneous immune-related adverse events (cirAEs) is associated with favorable outcomes among individuals with cancer who receive immune checkpoint inhibitor (ICI) treatment. Objective: To identify whether the presence of cirAEs and their subtypes subsequent to ICI administration is associated with enhanced cancer prognosis. Data Sources: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for publications examining the association between cirAE development during ICI treatment and subsequent cancer prognosis. The initial search was limited to English-language publications from database inception until December 31, 2022; a subsequent search was performed on May 21, 2023. Study Selection: Two reviewers independently scrutinized the identical articles and included those that constituted original research evaluating the association between cirAE development and cancer prognosis. Data Extraction and Synthesis: The search terms, study objectives, and methodological protocols were defined before study initiation. The aforementioned 2 reviewers performed data extraction independently and resolved discrepancies through agreement. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis and the Meta-analysis of Observational Studies in Epidemiology reporting guidelines. The protocol was prospectively registered with PROSPERO. Data analyses were conducted between May 21 and June 1, 2023. Main Outcomes and Measures: The major outcome end points were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were also conducted according to cirAE type, cancer type, geographic region, study design, and ICI type. Given the heterogeneity inherent in the included studies, a DerSimonian-Laird random-effects model was adopted. Results: This systematic review and meta-analysis included 23 studies with a total of 22 749 patients treated with ICIs. The occurrence of cirAEs was associated with improved OS (hazard ratio [HR], 0.61 [95% CI, 0.52-0.72]; P < .001) and PFS (HR, 0.52 [95% CI, 0.41-0.65]; P < .001). Consistent results were observed across all subgroups stratified by study design, geographic region, ICI type, and cancer type, aligning with the overall estimate of OS and PFS improvement. However, no statistically significant differences were identified in terms of PFS within studies conducted in the US. Conclusions and Relevance: In this systematic review and meta-analysis, the presence of cirAEs and their subtypes was associated with improved prognosis for individuals with cancer undergoing ICI treatment. These findings suggest that cirAEs may have useful prognostic value in ICI treatment.