Impact of Immune-Related Adverse Events on Survival in Patients With Gastrointestinal Cancer Treated With Immune Checkpoint Inhibitors: A Meta-Analysis.

Introduction: Immune-related adverse events (irAEs) stemming from off-target immune activation have been associated with improved survival outcomes in various cancers. Nonetheless, the influence of irAEs on survival among gastrointestinal (GI) cancer patients treated with immune checkpoint inhibitors (ICIs) remains ambiguous. The aim of this meta-analysis was to clarify the relationship between irAEs and survival outcomes in this patient cohort.

Methods: We systematically searched PubMed, Embase, and Web of Science to identify relevant observational studies with longitudinal data. Studies reported on overall survival (OS) or progression-free survival (PFS) among patients with GI cancer treated with ICIs, comparing those with irAEs with those without. We calculated pooled hazard ratios (HRs) and 95% confidence intervals (CIs) using a random-effects model to account for heterogeneity.

Results: Our analysis included 22 retrospective cohort studies comprising 2,935 patients; 1,142 (38.9%) experienced irAEs. The pooled analyses indicated a significant association between the occurrence of irAEs and improved OS (HR: 0.45, 95% CI 0.36-0.57, P < 0.001, I2 = 56%) and PFS (HR: 0.44, 95% CI 0.34-0.57, P < 0.001, I2 = 65%). Subgroup analyses supported the consistency of these findings across tumor location, study quality scores, follow-up duration, and analytical models, with no significant differences noted ( P for subgroup differences all >0.05).

Discussion: The presence of irAEs in patients with GI cancer receiving ICIs correlates with significantly better OS and PFS. This suggests that irAEs may be a potential biomarker for predicting treatment response.