Effect of antacids on the survival of patients with metastatic urothelial carcinoma treated with pembrolizumab

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=0.010, 0.018, and 0.012, 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=0.011), CSS (HR=1.45, 95% CI 1.09-1.93, P =0.011), and PFS (HR=1.35, 95% CI 1.05-1.73, P =0.020). 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. MicroAbstract Proton pump inhibitors (PPIs) can affect immune checkpoint inhibitors' efficacy in patients with metastatic urothelial carcinoma (mUC), while histamine-2 receptor antagonists (H2RAs) have been poorly evaluated. This retrospective multicenter study analyzed 404 patients with mUC. PPIs were significantly associated with worse survival of patients with mUC treated with pembrolizumab, while H2RAs did not. H2RAs can be an alternative during administration.