Healthcare utilization associated with immune-related adverse events in gastrointestinal malignancies: A systematic review and meta-analysis.

Abstract

366 Background: Immune checkpoint inhibitors (ICIs) improve outcomes across gastrointestinal (GI) malignancies but may increase healthcare utilization through severe immune-related adverse events (irAEs), hospitalization, corticosteroid exposure, and treatment discontinuation. We evaluated the pooled burden of severe toxicity associated with ICIs in GI malignancies. Methods: PubMed, Embase, and Cochrane databases were systematically searched for randomized and observational studies evaluating ICIs in colorectal, gastric/gastroesophageal, esophageal, hepatobiliary, pancreatic, and anal cancers. Outcomes included grade ≥3 treatment-related adverse events (TRAEs), treatment discontinuation, hospitalization, corticosteroid use, and toxicity-related mortality. A random-effects pooled proportion meta-analysis was performed to estimate incidence rates with 95% confidence intervals (CIs). Heterogeneity was assessed using I² statistics. Subgroup analyses compared ICI monotherapy versus combination regimens. Results: Eighteen studies involving 9,842 patients met inclusion criteria. The pooled incidence of grade ≥3 TRAEs with ICI-based therapy was 38.7% (95% CI, 33.1–44.5; I²=71%). Combination ICI regimens demonstrated significantly higher pooled grade ≥3 toxicity compared with ICI monotherapy (52.4% vs 24.8%). Treatment discontinuation due to toxicity occurred in 11.6% (95% CI, 8.9–14.7), while toxicity-related mortality occurred in 1.8% (95% CI, 1.1–2.7). Severe irAEs including colitis, hepatitis, pneumonitis, and endocrinopathies were major contributors to corticosteroid utilization, hospitalization, and treatment interruption. Combination regimens consistently demonstrated greater toxicity-related healthcare utilization than monotherapy approaches. Conclusions: ICI-based therapy in GI malignancies is associated with clinically significant toxicity-related healthcare utilization, particularly with combination regimens. Standardized irAE management pathways and proactive supportive care strategies may reduce preventable utilization while preserving the therapeutic benefit of immunotherapy.