厄洛替尼与贝伐单抗联合用药与厄洛替尼单药治疗晚期非小细胞肺癌（NSCLC）患者的疗效比较：一项系统评价和荟萃分析

Comparing Efficacy of Erlotinib and Bevacizumab Combination with Erlotinib Monotherapy in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): A Systematic Review and Meta-Analysis.

作者信息

Sakharkar Prashant, Kurup Sonali

机构信息

Department of Clinical and Administrative Sciences, College of Science, Health and Pharmacy, Roosevelt University, Schaumburg, IL 60173, USA.

Department of Pharmaceutical Sciences, College of Pharmacy, Ferris State University, Big Rapids, MI 49307, USA.

出版信息

Diseases. 2023 Oct 23;11(4):146. doi: 10.3390/diseases11040146.

The objective of this systematic review and meta-analysis was to assess and contrast the efficacy and safety of combining erlotinib and bevacizumab with erlotinib alone in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The authors searched databases such as PubMed, Medline, Scopus, and Cochrane Central Register of Controlled Trials for randomized control trials (RCTs) comparing erlotinib plus bevacizumab with erlotinib in NSCLC patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) were the outcomes of interest. The pooled hazard ratio (HR) and relative risk (RR) were estimated utilizing both fixed- and random-effect models. Methodological quality of the included studies was assessed using the Cochrane Risk of Bias tool. Nine studies comprising 1698 patients with NSCLC were included in this meta-analysis, of whom 850 were treated with erlotinib plus bevacizumab, and 848 with erlotinib. The erlotinib plus bevacizumab combination significantly prolonged PFS (HR, 0.62, 95% CI: 0.56, 0.70, < 0.00001) but did not show any significant improvement in OS (HR, 0.95; 95% CI: 0.83, 1.07, = 0.39) and ORR (HR, 1.10; 95% CI: 0.98, 1.24, = 0.09). Increased risks of hypertension (RR, 5.15; 95% CI: 3.59, 7.39; < 0.00001), proteinuria (RR, 10.54; 95% CI: 3.80, 29.20; < 0.00001) and grade 3 and higher AEs (RR, 2.09; 95% CI: 1.47, 2.97; < 0.00001) were observed with the erlotinib-plus-bevacizumab combination compared to erlotinib monotherapy. On subgroup analyses, the erlotinib plus bevacizumab combination improved PFS only. Combining erlotinib and bevacizumab has been shown to improve PFS in advanced NSCLC patients but did not show any significant OS and ORR benefits. Furthermore, risks of hypertension, proteinuria, and grade 3 or higher AEs were greater with the erlotinib-and-bevacizumab combination.

本系统评价和荟萃分析的目的是评估并对比厄洛替尼与贝伐单抗联合用药和单用厄洛替尼治疗晚期非小细胞肺癌（NSCLC）患者的疗效和安全性。作者检索了PubMed、Medline、Scopus和Cochrane对照试验中央注册库等数据库，以查找比较厄洛替尼联合贝伐单抗与单用厄洛替尼治疗NSCLC患者的随机对照试验（RCT）。总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和不良事件（AE）是关注的结局指标。采用固定效应模型和随机效应模型估计合并风险比（HR）和相对风险（RR）。使用Cochrane偏倚风险工具评估纳入研究的方法学质量。本荟萃分析纳入了9项研究，共1698例NSCLC患者，其中850例接受厄洛替尼联合贝伐单抗治疗，848例接受厄洛替尼治疗。厄洛替尼联合贝伐单抗显著延长了PFS（HR，0.62；95%CI：0.56，0.70；P<0.00001），但在OS（HR，0.95；95%CI：0.83，1.07；P=0.39）和ORR（HR，1.10；95%CI：0.98，1.24；P=0.09）方面未显示出任何显著改善。与单用厄洛替尼相比，厄洛替尼联合贝伐单抗治疗组高血压（RR，5.15；95%CI：3.59，7.39；P<0.00001）、蛋白尿（RR，10.54；95%CI：3.80，29.20；P<0.00001）以及3级及以上不良事件（RR，2.09；95%CI：1.47，2.97；P<0.00001）的风险增加。亚组分析显示，厄洛替尼联合贝伐单抗仅改善了PFS。已证明厄洛替尼与贝伐单抗联合用药可改善晚期NSCLC患者的PFS，但在OS和ORR方面未显示出任何显著益处。此外，厄洛替尼与贝伐单抗联合用药时，高血压、蛋白尿以及3级或更高等级不良事件的风险更高。