Effect of Antacids on the Survival of Patients With Metastatic Urothelial Carcinoma Treated With Pembrolizumab

Takanori Sekito, Kensuke Bekku, Satoshi Katayama, Tomofumi Watanabe, Ichiro Tsuboi, Kasumi Yoshinaga, Yuki Maruyama, Tomoaki Yamanoi, Tatsushi Kawada, Yusuke Tominaga, Takuya Sadahira, Takehiro Iwata, Shingo Nishimura, Norihiro Kusumi, Kohei Edamura, Tomoko Kobayashi, Kyohei Kurose, Takaharu Ichikawa, Yoshiyuki Miyaji, Koichiro WadaYasuyuki Kobayashi, Motoo Araki

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Introduction: Concomitant medications can affect the efficacy of immune checkpoint inhibitors. The association between histamine-2 receptor antagonists (H2RAs), major antacids similar to proton pump inhibitors (PPIs), and the efficacy of pembrolizumab for metastatic urothelial carcinoma (mUC) treatment has been poorly evaluated. We evaluated the impact of PPIs and H2RAs on oncological outcomes in mUC patients treated with pembrolizumab. Patients and Methods: This retrospective multicenter study included patients with mUC treated with pembrolizumab. Patients prescribed PPIs or H2RAs within 30 days before and after the initial administration were extracted. The overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and objective response rates (ORR) were assessed. Kaplan–Meier survival curve analysis and multivariable Cox proportional hazard models were employed to assess the association between PPIs or H2RAs and survival outcomes. Results: Overall, 404 patients were eligible for this study; 121 patients (29.9%) used PPIs, and 34 (8.4%) used H2RAs. Kaplan–Meier analysis showed significantly worse OS, CSS, and PFS in patients using PPIs compared to no PPIs (P = .010, .018, and .012, respectively). In multivariable analyses, the use of PPIs was a significant prognostic factor for worse OS (HR = 1.42, 95% CI 1.08-1.87, P = .011), CSS (HR = 1.45, 95% CI 1.09-1.93, P = .011), and PFS (HR = 1.35, 95% CI 1.05-1.73, P = .020). PPIs were not associated with ORRs. The use of H2RAs was not associated with survival or ORRs. Conclusion: PPIs were significantly associated with worse survival of patients with mUC treated with pembrolizumab, and H2RAs could be an alternative during administration. Both the oncological and gastrointestinal implications should be carefully considered when switching these antacids.

Original languageEnglish
Article number102097
JournalClinical Genitourinary Cancer
Volume22
Issue number4
DOIs
Publication statusPublished - Aug 2024
Externally publishedYes

Keywords

  • Antacids
  • Immune checkpoint inhibitors
  • Neoplasm metastasis
  • Survival
  • Transitional cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Urology

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