Effects of Proton Pump Inhibitors on Survival Outcomes in Patients with Metastatic or Unresectable Urothelial Carcinoma Treated with Pembrolizumab

• Published in: Biological & pharmaceutical bulletin Vol. 45; no. 5; pp. 590 - 595
• Main Authors: Kunimitsu, Yoko, Morio, Kayoko, Hirata, Sachi, Yamamoto, Kazuhiro, Omura, Tomohiro, Hara, Takuto, Harada, Kenichi, Fujisawa, Masato, Yano, Ikuko
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01-05-2022; Japan Science and Technology Agency
• Subjects: Antibodies, Monoclonal, Humanized; Bladder cancer; Cancer; Carcinoma, Transitional Cell - drug therapy; Digestive system; Female; gut microbiome; Humans; Immune checkpoint inhibitors; Immunotherapy; Intestinal microflora; Male; Medical prognosis; Metastases; Metastasis; Microbiomes; Microbiota; Monoclonal antibodies; Patients; Pembrolizumab; proton pump inhibitor; Proton Pump Inhibitors; Retrospective Studies; Survival; Targeted cancer therapy; Tumors; Urinary Bladder Neoplasms; Urothelial carcinoma; pembrolizumab; gut microbiome; urothelial carcinoma; proton pump inhibitor; survival
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b21-00939

The gut microbiome influences tumor response to immune checkpoint inhibitors (ICIs). The proton pump inhibitors (PPI) significantly impair diversity of the gut microbiota and can affect the efficacy of ICIs. Therefore, the present study aimed to evaluate the influence of PPI on survival in patients with metastatic or unresectable urothelial carcinoma receiving pembrolizumab. We conducted a retrospective cohort study of patients with metastatic or unresectable urothelial carcinoma receiving pembrolizumab. The use of PPI was defined as any administration for ≥30 d within 60 d prior and/or 30 d after treatment initiation. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method, and Cox proportional hazards regression analysis was performed to investigate prognostic factors based on patient characteristics. Seventy-nine patients were included in the analysis, and 34 patients (43.0%) received PPI. There were no significant differences in OS and PFS between PPI users and nonusers (median OS: 8.2 months vs. 11.2 months, hazard ratio (HR): 1.36, 95% confidence interval (CI): 0.75–2.42, p = 0.296; median PFS: 3.5 months vs. 5.1 months, HR: 1.63, 95% CI: 0.95–2.80, p = 0.069). In the multivariable analysis, PPI use was not associated with OS (HR 0.80, 95% CI 0.40–1.56, p = 0.526) or PFS (HR 1.44, 95% CI 0.79–2.60, p = 0.233). In conclusion, the estimated effect size of PPI use on survival in Japanese patients with metastatic or unresectable urothelial carcinoma treated with pembrolizumab was not reproducible.