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

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.