Du Xin, Liu Wei, Chen Ken, Wang Ziyu, Li Xinyi, Yang Li, Xie Xiaohui
School of Pharmaceutical Sciences, Peking University, Beijing, China.
Department of Pharmacy, Peking University Third Hospital, Beijing, China.
Front Pharmacol. 2022 Jun 20;13:796538. doi: 10.3389/fphar.2022.796538. eCollection 2022.
The use of gastric acid suppressants (GASs) has an influence on the exposure of some epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and therefore may affect the effectiveness and safety of EGFR-TKIs. The impact of GASs, including proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (HRAs), on the effectiveness and safety of EGFR-TKIs remains unclear. We conducted a meta-analysis to explore the impact of GASs on the effectiveness and safety of EGFR-TKIs in non-small cell lung cancer (NSCLC) patients. We searched the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases thoroughly from inception to 2nd February 2021, including the studies for NSCLC patients who used GASs, offering the adjusted hazard ratio (HR) of effectiveness outcomes such as overall survival (OS) and progression-free survival (PFS) or adjusted odds ratio (OR) of the adverse drug reaction (ADRs), and the results were calculated with a random effect. Two researchers independently screened the literature, extracted data, and evaluated the quality. Stata 15.0 was used for meta-analysis. Twelve studies were finally included. Nine of them were cohort studies, and three of them were case-control studies. For effectiveness outcomes, the use of GASs was associated with shorter PFS (HR 1.66 [1.40, 1.98]) and OS (HR 1.50 [1.31, 1.72]), and the use of PPIs was associated with shorter OS (HR 1.56 [1.21, 2.02]), regardless of the overlap time and type of EGFR-TKIs. For safety outcomes, the use of GASs (OR 1.98 [1.19, 3.31]) or PPIs (OR 1.91 [1.17, 3.12]) were both associated with an increased risk of hepatotoxicity. The concomitant use of GASs is associated with shorter PFS and OS for NSCLC patients taking EGFR-TKIs and is also associated with a higher risk of hepatotoxicity. The co-administration of GASs should be avoided; if they cannot be avoided, HRAs is a better choice. (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235018), identifier (PROSPERO 2021 CRD42021235018).
使用胃酸抑制剂（GASs）会对某些表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）的暴露产生影响，因此可能会影响EGFR-TKIs的有效性和安全性。包括质子泵抑制剂（PPIs）和组胺2型受体拮抗剂（HRAs）在内的GASs对EGFR-TKIs有效性和安全性的影响尚不清楚。我们进行了一项荟萃分析，以探讨GASs对非小细胞肺癌（NSCLC）患者使用EGFR-TKIs的有效性和安全性的影响。我们全面检索了PubMed、Embase、Cochrane图书馆、中国知网和万方数据库，检索时间从建库至2021年2月2日，纳入了使用GASs的NSCLC患者的研究，提供了有效性结局如总生存期（OS）和无进展生存期（PFS）的调整后风险比（HR）或药物不良反应（ADRs）的调整后比值比（OR），结果采用随机效应模型计算。两名研究人员独立筛选文献、提取数据并评估质量。使用Stata 15.0进行荟萃分析。最终纳入12项研究。其中9项为队列研究，3项为病例对照研究。对于有效性结局，无论EGFR-TKIs的重叠时间和类型如何，使用GASs与较短的PFS（HR 1.66 [1.40, 1.98]）和OS（HR 1.50 [1.31, 1.72]）相关，使用PPIs与较短的OS（HR 1.56 [1.21, 2.02]）相关。对于安全性结局，使用GASs（OR 1.98 [1.19, 3.31]）或PPIs（OR 1.91 [1.17, 3.12]）均与肝毒性风险增加相关。对于服用EGFR-TKIs的NSCLC患者，同时使用GASs与较短的PFS和OS相关，也与较高的肝毒性风险相关。应避免同时使用GASs；如果无法避免，HRAs是更好的选择。（https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235018），标识符（PROSPERO 2021 CRD42021235018）
