Abstract：
BACKGROUND: 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.
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：合并用药会影响免疫检查点抑制剂的疗效。组胺-2受体拮抗剂（H2RAs），类似于质子泵抑制剂（PPI）的主要抗酸剂，pembrolizumab治疗转移性尿路上皮癌（mUC）的疗效评估不佳。我们评估了PPI和H2RAs对pembrolizumab治疗的mUC患者肿瘤预后的影响。
方法：这项回顾性多中心研究包括接受派姆单抗治疗的mUC患者。患者在初次给药之前和之后30天内开出PPI或H2RA。总生存期（OS），癌症特异性生存率（CSS），无进展生存期（PFS），并评估客观缓解率(ORR).采用Kaplan-Meier生存曲线分析和多变量Cox比例风险模型来评估PPI或H2RAs与生存结果之间的关联。
结果：总体而言，404名患者符合本研究的条件；121名患者（29.9%）使用PPI，和34（8.4％）使用H2RAs。Kaplan-Meier分析显示操作系统明显更差，CSS,与无PPI相比，使用PPI的患者的PFS和PFS（分别为P=.010、.018和.012）。在多变量分析中，使用PPI是OS恶化的显著预后因素(HR=1.42,95%CI1.08-1.87,P=.011),CSS（HR=1.45，95%CI1.09-1.93，P=0.011），和PFS（HR=1.35，95%CI1.05-1.73，P=0.020）。PPI与ORR无关。H2RAs的使用与生存率或ORR无关。
结论：PPI与pembrolizumab治疗的mUC患者的生存率下降显著相关，和H2RAs可以是在给药期间的替代方案。切换这些抗酸剂时，应仔细考虑肿瘤和胃肠道的影响。
方法：这项回顾性多中心研究包括接受派姆单抗治疗的mUC患者。患者在初次给药之前和之后30天内开出PPI或H2RA。总生存期（OS），癌症特异性生存率（CSS），无进展生存期（PFS），并评估客观缓解率(ORR).采用Kaplan-Meier生存曲线分析和多变量Cox比例风险模型来评估PPI或H2RAs与生存结果之间的关联。
结果：总体而言，404名患者符合本研究的条件；121名患者（29.9%）使用PPI，和34（8.4％）使用H2RAs。Kaplan-Meier分析显示操作系统明显更差，CSS,与无PPI相比，使用PPI的患者的PFS和PFS（分别为P=.010、.018和.012）。在多变量分析中，使用PPI是OS恶化的显著预后因素(HR=1.42,95%CI1.08-1.87,P=.011),CSS（HR=1.45，95%CI1.09-1.93，P=0.011），和PFS（HR=1.35，95%CI1.05-1.73，P=0.020）。PPI与ORR无关。H2RAs的使用与生存率或ORR无关。
结论：PPI与pembrolizumab治疗的mUC患者的生存率下降显著相关，和H2RAs可以是在给药期间的替代方案。切换这些抗酸剂时，应仔细考虑肿瘤和胃肠道的影响。
