Impact of the Use of Proton Pump Inhibitors on Pembrolizumab Effectiveness for Advanced Urothelial Carcinoma

Ikko Tomisaki; Mirii Harada; Akinori Minato; Yujiro Nagata; Rieko Kimuro; Katsuyoshi Higashijima; Kenichi Harada; Naohiro Fujimoto

doi:10.21873/anticanres.15638

Impact of the Use of Proton Pump Inhibitors on Pembrolizumab Effectiveness for Advanced Urothelial Carcinoma

Anticancer Res. 2022 Mar;42(3):1629-1634. doi: 10.21873/anticanres.15638.

Authors

Ikko Tomisaki¹, Mirii Harada², Akinori Minato², Yujiro Nagata², Rieko Kimuro², Katsuyoshi Higashijima², Kenichi Harada², Naohiro Fujimoto²

Affiliations

¹ Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan ikko@med.uoeh-u.ac.jp.
² Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan.

PMID: 35220261
DOI: 10.21873/anticanres.15638

Abstract

Background/aim: This study aimed to clarify the impact of proton pump inhibitors (PPIs) on oncological outcomes in patients who received pembrolizumab for advanced urothelial carcinoma (UC).

Patients and methods: Forty advanced UC patients treated with pembrolizumab were retrospectively reviewed and divided into two groups (PPI: 15 patients; without PPI: 25 patients). Tumor response and survival were compared between these groups. The factors associated with survival were also investigated.

Results: The objective response rate was significantly lower in the group with PPIs compared with the group without PPIs. Both progression-free survival (PFS) and overall survival (OS) were significantly shorter in the group with PPIs than in the group without PPIs. The use of PPIs was a significant predictor of poor PFS and OS in multivariate analysis.

Conclusion: The use of PPIs was negatively associated with tumor response and survival in patients with advanced UC treated with pembrolizumab.

Keywords: Proton pump inhibitors; antibiotics; gut microbiota; immune checkpoint inhibitors; pembrolizumab; urothelial carcinoma.

MeSH terms

Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized / adverse effects
Antibodies, Monoclonal, Humanized / therapeutic use*
Carcinoma / drug therapy*
Carcinoma / immunology
Carcinoma / mortality
Carcinoma / pathology
Female
Humans
Immune Checkpoint Inhibitors / adverse effects
Immune Checkpoint Inhibitors / therapeutic use*
Male
Progression-Free Survival
Proton Pump Inhibitors / adverse effects
Proton Pump Inhibitors / therapeutic use*
Retrospective Studies
Risk Assessment
Risk Factors
Time Factors
Urinary Bladder Neoplasms / drug therapy*
Urinary Bladder Neoplasms / immunology
Urinary Bladder Neoplasms / mortality
Urinary Bladder Neoplasms / pathology

Substances

Antibodies, Monoclonal, Humanized
Immune Checkpoint Inhibitors
Proton Pump Inhibitors
pembrolizumab