Detrimental impact of gastric acid suppressants on vascular endothelial growth factor receptor tyrosine kinase inhibitors efficacy: evidence from a systematic review and meta-analysis

This meta-analysis evaluated theprevalence of gastric acid suppressants (GASs) in patients receiving vascularendothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) andexplored drug-drug interactions (DDIs). PubMed, Embase, and Cochrane Library were searched upto 20 October 2024. Studies comparing VEGFR-TKIs monotherapy versus VEGFR-TKIswith GASs, reporting pharmacodynamic (PD), pharmacokinetic (PK), or adverseevents (AEs), were analyzed using random-effects models. Subgroups includedcancer types and VEGFR-TKI types. 24 studies comprising 6,406 patients were included. Theprevalence of GASs use in VEGFR-TKIs users was 40% (95% CI 31-50%). GASssignificantly impaired survival, increasing mortality risk by 29% (OS HR 1.29,95% CI 1.14-1.45) and progression risk by 31% (PFS HR 1.31, 95% CI 1.06-1.61).PK analyses revealed clinically meaningful exposure reductions (AUC0-24GMR 0.78, 90% CI 0.65-0.94; Cmax GMR 0.80, 90% CI 0.70-0.91). AEincidence (except vomiting) did not differ between groups. GASs may reduce the efficacy of mosttypes of VEGFR-TKIs by decreasing their bioavailability, thereby having adetrimental effect on patient survival outcomes. It is recommended to givepriority to H2 receptor antagonists (H2RAs) and monitor blood drugconcentrations to optimize efficacy. www.crd.york.ac.uk/prospero identifier CRD42024597729.