Impact of gastric acid suppressants on oral protein kinase inhibitor efficacy: A systematic review and meta-analysis of plasma concentrations and survival outcomes

Introduction While the co-administration of oral protein kinase inhibitors (PKIs) and gastric acid suppressants (GASs) is widespread, the impact of GASs on the pharmacokinetics and survival outcomes of PKIs has remained systematically uninvestigated. The present study aimed to address this knowledge gap and to verify whether PKI plasma concentrations can predict these interactions. Methods MEDLINE and CENTRAL databases were searched until April 4, 2025. We included studies of PKIs where their plasma concentrations and the survival outcomes of participants taking PKIs with GASs. All studies eligible for this analysis were assessed using the appropriate risk-of-bias tool. For the meta-analysis, we estimated the ratio of the mean plasma concentrations and the hazard ratios of survival outcomes. Results This meta-analysis included 17,339 participants from 38 studies, including 11 PKIs. Our results revealed that the co-administration of PKIs with GASs led to a concurrent decrease in plasma concentrations and a shorter OS in 8 out of 11 PKIs, as well as a shorter PFS in 10 PKIs. Conclusions We found that changes in the plasma concentrations of PKIs administered with GASs could predict the changes in survival outcomes in cancer patients. One major limitation of this meta-analysis was that 68% of the eligible studies had a retrospective design.