Concomitant Proton Pump Inhibitor Use and Survival in Urothelial Carcinoma Treated with Atezolizumab

阿替唑单抗 医学 危险系数 内科学 肿瘤科 质子抑制剂泵 人口 癌症 膀胱癌 相伴的 化疗 随机对照试验 置信区间 免疫疗法 无容量 环境卫生
作者
Ashley M. Hopkins,Ganessan Kichenadasse,Christos S. Karapetis,Andrew Rowland,Michael J. Sorich
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
卷期号:26 (20): 5487-5493 被引量:77
标识
DOI:10.1158/1078-0432.ccr-20-1876
摘要

Emerging evidence indicates that gut microbiota dysbiosis can reduce the effectiveness of immune checkpoint inhibitors (ICI). Proton pump inhibitors (PPI) are known to induce gut microbiota changes. However, little is known on the effects of PPIs on outcomes with ICI therapy, and it has not been explored in urothelial cancer treatment.Individual-participant data from the advanced urothelial cancer trials, IMvigor210 (single-arm atezolizumab trial, n = 429) and IMvigor211 (phase III randomized trial of atezolizumab vs. chemotherapy, n = 931) were pooled in a Cox proportional hazard analysis assessing the association between PPI use and overall survival (OS) and progression-free survival (PFS). PPI use was defined as any PPI administration between 30 days prior and 30 days after treatment initiation.Of the 1,360 participants, 471 (35%) received a PPI within the 60-day window. PPI use was associated with significantly worse OS [HR (95% confidence interval (CI)) = 1.52 (1.27-1.83), P < 0.001] and PFS [1.38 (1.18-1.62), P < 0.001] with atezolizumab, but not chemotherapy (P > 0.05). In the randomized cohort of IMvigor211, the OS treatment effect [HR (95% CI)] of atezolizumab versus chemotherapy was 1.04 (0.81-1.34) for PPI users, compared with 0.69 (0.56-0.84) for PPI nonusers (Pinteraction = 0.013). Similar associations were noted in the PD-L1 IC2/3 population.This study indicates PPI use is a negative prognostic marker in advanced urothelial carcinoma treated with ICI therapy, but not chemotherapy. Furthermore, the analysis suggests PPIs influence the magnitude of ICI efficacy, and this warrants further investigation.
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