Effect of proton pump inhibitors on the clinical outcomes of PD-1/PD-L1 inhibitor in solid cancer patients

Abstract

Background: Some concomitant drugs may affect the efficacy of programmed death protein-1/ligand-1 (PD-1/L1) inhibitors. Among the various concomitant drugs, proton-pump inhibitors (PPI) have attracted some attention but have not reached a conclusion. We conducted a meta-analysis to evaluate the impact of PPIs on the survival of cancer patients treated with PD-1/L1 inhibitors. Material/methods: Related databases and conferences reports were searched. Studies that reported the relationship between PPI use and clinical outcomes of PD-1/L1 inhibitors were included. Meta-analysis was conducted to obtain pooled hazard ratios (HR)s with 95% confidence interval (CI). Results: Eight studies involving 4869 cancer patients were included. Meta-analysis showed that PPI use was associated with worse overall survival (OS) (HR = 1.43, 95% CI 1.32-1.56), worse progression free survival (PFS) (HR = 1.30, 95% CI 1.20-1.40), and decreased objective response (odds ratio = 0.71, 95% CI 0.58-0.87) in cancer patients receiving PD-1/L1 inhibitors. Neither cancer type nor therapy type affected the effect of concomitant PPIs on the OS and PFS. In the subgroup of studies with a population size <500, PPIs did not reduce the OS, but the PFS. Only 1 single-center study was conducted, showing that PPI use did not affect the OS and PFS. There was no evidence of publication bias among included studies. Conclusion: Concomitant PPI use was correlated with worse clinical outcomes in cancer patients treated by PD-1/L1 inhibitors. Further prospective clinical and experimental studies are needed to confirm the effect and mechanism of PPI in worsening the clinical outcome of PD-1/L1 inhibitors.