EGFR 酪氨酸激酶抑制剂在可手术非小细胞肺癌辅助治疗中的疗效：一项荟萃分析。

Efficacy of EGFR Tyrosine Kinase Inhibitors in the Adjuvant Treatment for Operable Non-small Cell Lung Cancer by a Meta-Analysis.

机构信息

Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

出版信息

Chest. 2016 Jun;149(6):1384-92. doi: 10.1016/j.chest.2015.12.017. Epub 2015 Dec 24.

DOI:10.1016/j.chest.2015.12.017

PMID:26836897

Abstract

BACKGROUND

The role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the adjuvant treatment of non-small cell lung cancer (NSCLC) has not been well-established. Our meta-analysis aimed to determine whether the administration of EGFR-TKIs could improve the outcomes of patients with NSCLC undergoing complete resection.

METHODS

We comprehensively searched databases and extracted data from eligible studies. Disease-free survival (DFS) and overall survival (OS) with hazard ratios (HRs) as well as disease relapse with odds ratios (OR) were calculated using random and/or fixed-effects models. Meta-regression analysis and test for interaction between subgroups were also carried out.

RESULTS

A total of 1,960 patients in five studies were included. Adjuvant EGFR-TKI treatment was associated with a significant benefit on DFS (HR, 0.63; 95% CI, 0.41-0.99), corresponding to an absolute benefit of 3.1% at 3 years, yet with significant heterogeneity (I(2) = 83.4%, P < .001). The survival benefit was superior (Pinteraction = .03) in studies with more than an 18-month median treatment duration. EGFR mutation rate was also identified as a source of heterogeneity (P = .017). In the population with EGFR mutations, HR for DFS was 0.48 (95% CI, 0.36-0.65), corresponding to an absolute benefit of 9.5% at 3 years, with a reduced risk of distant metastasis (OR, 0.71; 95% CI, 0.56-0.92). Adjuvant EGFR-TKI treatment resulted in a marginally statistically significant benefit on OS (HR, 0.72; 95% CI, 0.49-1.06). The rate of overall grade 3 or greater adverse events was 42.3% (95% CI, 39.1-45.6).

CONCLUSIONS

Adjuvant EGFR-TKI treatment may enhance disease-free survival and reduce the risk of distant metastasis in patients with EGFR-mutant NSCLC undergoing complete resection.

摘要

背景

表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）在非小细胞肺癌（NSCLC）辅助治疗中的作用尚未得到充分证实。我们的荟萃分析旨在确定 EGFR-TKI 的应用是否可以改善完全切除的 NSCLC 患者的结局。

方法

我们全面检索数据库并提取符合条件的研究中的数据。使用随机和/或固定效应模型计算无病生存期（DFS）和总生存期（OS）的风险比（HR）以及疾病复发的比值比（OR）。还进行了荟萃回归分析和亚组间交互检验。

结果

五项研究共纳入 1960 例患者。辅助 EGFR-TKI 治疗与 DFS 显著获益相关（HR，0.63；95%CI，0.41-0.99），3 年时绝对获益为 3.1%，但存在显著异质性（I2=83.4%，P<.001）。在治疗中位时间超过 18 个月的研究中，生存获益更优（P 交互=.03）。EGFR 突变率也是异质性的来源（P=.017）。在 EGFR 突变人群中，DFS 的 HR 为 0.48（95%CI，0.36-0.65），3 年时绝对获益为 9.5%，远处转移风险降低（OR，0.71；95%CI，0.56-0.92）。辅助 EGFR-TKI 治疗对 OS 有一定统计学意义的获益（HR，0.72；95%CI，0.49-1.06）。总体 3 级或更高级别的不良事件发生率为 42.3%（95%CI，39.1-45.6）。