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 the prevalence of gastric acid suppressants (GASs) in patients receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) and explored drug-drug interactions (DDIs). PubMed, Embase, and Cochrane Library were searched upto 20 October 2024. Studies comparing VEGFR-TKIs monotherapy versus VEGFR-TKIs with GASs, reporting pharmacodynamic (PD), pharmacokinetic (PK), or adverse events (AEs), were analyzed using random-effects models. Subgroups included cancer types and VEGFR-TKI types. 24 studies comprising 6,406 patients were included. The prevalence of GASs use in VEGFR-TKIs users was 40% (95% CI 31–50%). GASs significantly 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 (AUC_0–24GMR 0.78, 90% CI 0.65–0.94; C_max GMR 0.80, 90% CI 0.70–0.91). AE incidence (except vomiting) did not differ between groups. GASs may reduce the efficacy of most types of VEGFR-TKIs by decreasing their bioavailability, thereby having a detrimental effect on patient survival outcomes. It is recommended to give priority to H2 receptor antagonists (H2RAs) and monitor blood drug concentrations to optimize efficacy. www.crd.york.ac.uk/prospero identifier CRD42024597729