Antibiotic Use Linked to Worse Outcomes in Patients With Gastrointestinal and Liver Cancer on Immune Checkpoint Inhibitors: A Meta-Analysis.

Abstract

Immune checkpoint inhibitors (ICIs) are increasingly used in gastrointestinal and liver cancers. However, antibiotic-induced gut microbiota disruption may influence ICI effectiveness. The objective of this study was to evaluate association between antibiotic use and clinical outcomes among patients with gastrointestinal and liver cancers receiving ICI therapy. In this meta-analysis, we searched studies involving adults with gastrointestinal or liver cancers treated with ICIs, comparing outcomes between patients with and without antibiotic use. Eligible studies reported hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for overall survival (OS), progression-free survival (PFS), objective response rate, or disease control rate. Random-effects models were used for pooled analyses. Twenty-eight studies were included. Antibiotic use was associated with worse OS (HR 1.56; 95% CI: 1.23-1.98; I2 = 87.3%), PFS (HR 1.48; 95% CI: 1.15-1.90; I2 = 88.3%), and disease control rate (OR 0.55; 95% CI: 0.33-0.90; I2 = 65.0%), but no significant difference in objective response rate (OR 1.01; 95% CI: 0.78-1.31; I2 = 0%). Results were consistent in subgroup analyses by ICI type and timing of antibiotic administration. Antibiotic use was associated with worse OS and PFS in hepatocellular carcinoma (HR for OS: 1.49; 95% CI: 1.24-1.79; HR for PFS: 1.25; 95% CI: 1.01-1.56) and upper gastrointestinal cancers (HR for OS: 2.40; 95% CI: 1.48-3.90; HR for PFS: 2.15; 95% CI: 1.18-3.91), whereas colorectal cancer studies showed improved OS (HR: 0.58; 95% CI: 0.45-0.75). Antibiotic use is associated with worse outcomes in patients with gastrointestinal or liver cancer receiving ICIs and should be carefully justified. Prospective studies are needed to validate these results.