Comparative safety of immune checkpoint inhibitor–chemotherapy regimens across multiple tumor types: A systematic review and network meta-analysis.

Abstract

e14571 Background: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become standard first-line treatment for multiple solid tumors, yet their safety profiles vary across therapeutic agents and tumor types. This systematic review and network meta-analysis (NMA) compared the safety of ICI plus chemotherapy regimens across multiple tumor types, particularly focusing on immune-related adverse events (irAEs). Methods: We systematically searched PubMed, Embase, and Web of Science for eligible phase III randomized controlled trials (RCTs) published between January 1, 2015, and November 30, 2025, that evaluated first-line ICI plus chemotherapy regimens in advanced solid tumors. The primary outcome was the grade ≥3 irAEs; additional outcomes included the all-grade irAEs. An NMA was performed estimating odds ratios (ORs) with 95% credibility intervals (CrI) and ranking regimens using Bayesian ranking probabilities. This study was registered with PROSPERO (CRD420251239812). Results: A total of 58 phase III RCTs were included, comprising 36664 patients and regimens combining chemotherapy with 20 distinct ICIs across multiple tumor types including lung, gastric/gastroesophageal junction, esophageal, breast, urothelial, nasopharyngeal, biliary tract, and head and neck squamous cell cancers. For grade ≥3 irAEs, cumulative ranking probabilities showed that top three safest ICI regimens were adebrelimab (47.0%), avelumab (22.0%) and finotonlimab (21.1%), with pooled OR versus chemotherapy alone of 1.62 (95% CrI 0.28–9.83), 2.78 (95% CrI 0.45–16.08) and 3.38 (95% CrI 0.42-37.26), respectively. Regarding all-grade irAEs, cumulative ranking probabilities identified avelumab as most likely to rank first (47.3%), followed by retifanlimab (42.3%) and adebrelimab (31.0%), with pooled OR versus chemotherapy alone of 1.54 (95% CrI 0.61–4.04), 1.61 (95% CrI 0.62–4.33) and 1.86 (95% CrI 0.69–4.96), respectively, showing better safety profile than other regimens. Conclusions: This study identifies clinically meaningful differences in safety profiles among ICI plus chemotherapy regimens across multiple solid tumors.