Jun Tomi, Ozbek Umut, Dharmapuri Sirish, Hardy-Abeloos Camille, Zhu Huili, Lin Jung-Yi, Personeni Nicola, Pressiani Tiziana, Nishida Naoshi, Lee Pei-Chang, Lee Chieh-Ju, Hildebrand Hannah, Nimkar Neil, Paul Sonal, Fessas Petros, Naeem Muntaha, Bettinger Dominik, Khan Uqba, Saeed Anwaar, Huang Yi-Hsiang, Kudo Masatoshi, Rimassa Lorenza, Marron Thomas U, Pinato David J, Ang Celina
Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ther Adv Med Oncol. 2021 Apr 28;13:17588359211010937. doi: 10.1177/17588359211010937. eCollection 2021.
Antibiotic exposure has been associated with worse outcomes with immune checkpoint inhibitors (ICIs) in cancer patients, likely due to disruption of the gut microbiome. Other commonly prescribed medications, such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs), are also known to disrupt the microbiome, but data on their association with ICI outcomes are conflicting.
We conducted a retrospective, multicenter, international cohort study including 314 hepatocellular carcinoma (HCC) patients treated with ICIs from 2017 to 2019 to assess the association between PPI or H2RA exposure (up to 30 days before ICI) and overall survival. Secondary outcomes included overall response rate (ORR) and development of any treatment-related adverse events (AEs).
Baseline PPI/H2RA exposure was not associated with overall survival in univariable (HR 1.01, 95% CI 0.75-1.35) or multivariable analysis (HR 0.98, 95% CI 0.71-1.36). Baseline PPI/H2RA exposure was not associated with either ORR (OR 1.32, 95% CI 0.66-2.65) or AEs (OR 1.07, 95% CI 0.54-2.12) in multivariable analysis.
Our results suggest that exposure to PPI/H2RA prior to ICIs does not adversely affect outcomes in HCC patients.
抗生素暴露与癌症患者使用免疫检查点抑制剂（ICI）的预后较差有关，这可能是由于肠道微生物群受到破坏。其他常用药物，如质子泵抑制剂（PPI）和组胺-2受体拮抗剂（H2RA），也已知会破坏微生物群，但关于它们与ICI预后关联的数据相互矛盾。
我们进行了一项回顾性、多中心、国际队列研究，纳入了2017年至2019年接受ICI治疗的314例肝细胞癌（HCC）患者，以评估PPI或H2RA暴露（ICI前最多30天）与总生存期之间的关联。次要结局包括总缓解率（ORR）和任何治疗相关不良事件（AE）的发生情况。
在单变量分析（HR 1.01，95%CI 0.75-1.35）或多变量分析（HR 0.98，95%CI 0.71-1.36）中，基线PPI/H2RA暴露与总生存期均无关联。在多变量分析中，基线PPI/H2RA暴露与ORR（OR 1.32，95%CI 0.66-2.65）或AE（OR 1.07，95%CI 0.54-2.12）均无关联。
我们的结果表明，在ICI治疗前使用PPI/H2RA不会对HCC患者的预后产生不利影响。
