Safety Profiles of Immune Checkpoint Inhibitor Strategies in Gastrointestinal Cancers and Their Association With Clinical Outcomes: A Systematic Review and Meta-Analysis.

Authors

Jing Lei, Yiyi Yu, Qing Liu, Ningping Zhang, Yi Wang, Yating Yang, Tianshu Liu, Minzhi Lv

Published in

Cancer medicine. Volume 15. Issue 10. Pages e72357.

Abstract

Immune checkpoint inhibitors (ICIs) are increasingly used in patients with gastrointestinal cancer (GIC). However, ICI-associated adverse event (AE) profiles in GIC remain poorly characterized, and whether AE incidence is associated with clinical outcomes is unclear.
Randomized controlled trials (RCTs) were identified through February 2025. Primary outcomes included treatment-related AEs (TRAEs) and immune-related AEs (irAEs) (any grade/Grade 3+). Single-arm random-effects meta-analysis pooled AE incidences; risk ratios (RRs) compared toxicity across ICI regimens. Digitized Kaplan-Meier curves reconstructed survival data for pooled analysis and Cox models. Weighted Spearman's tests assessed correlations between AE incidences and median overall survival (OS)/progression-free survival (PFS).
Forty RCTs enrolling 10,233 patients investigated ICI monotherapy, dual-ICI therapy, and ICI combination regimens. Pooled any-grade TRAE incidences were 68.0% (monotherapy, 95% CI: 60%-76%, I² = 97.4%, p < 0.001), 87.0% (dual therapy, 95% CI: 73%-100%, I² = 98.0%, p < 0.001), and 90.0% (combination therapy, 95% CI: 83%-96%, I² = 94.6%, p < 0.001). IrAE incidences reached 24.0% (monotherapy, 95% CI: 18%-29%, I² = 67.2%, p < 0.05) and 37.0% (combination therapy, 95% CI: 25%-49%, I² = 98.8%, p < 0.001). Relative to monotherapy, dual-ICI therapy elevated any-grade (RR = 1.28, 95% CI: 1.05-1.55) and grade ≥ 3 TRAEs (RR = 2.71, 95% CI: 1.84-3.99); ICI combination therapy increased any-grade (RR = 1.32, 95% CI: 1.15-1.51) and grade ≥ 3 TRAEs (RR = 2.98, 95% CI: 2.30-3.87). Any-grade TRAEs moderately correlated with median OS (R = 0.46, p < 0.001) and PFS (R = 0.50, p < 0.001). Any-grade irAEs strongly correlated with median OS (R = 0.90, p < 0.001) and moderately with PFS (R = 0.57, p < 0.001).
While AE incidence is high among GIC patients receiving ICIs, most events are low-grade. Dual-ICI and ICI-based combination therapies carry higher TRAE and irAE risks than monotherapy. At the trial level, higher non-severe irAE incidence correlated with favorable survival outcomes; this exploratory ecological association does not apply to individual patients.
This study was registered on International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202230144).

PMID:
42885207
Bibliographic data and abstract were imported from PubMed on 16 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.