表皮生长因子受体（EGFR）特定突变与临床特征对 EGFR 突变型肺癌患者接受 EGFR 酪氨酸激酶抑制剂与化疗治疗后结局的影响：一项荟萃分析。

Impact of Specific Epidermal Growth Factor Receptor (EGFR) Mutations and Clinical Characteristics on Outcomes After Treatment With EGFR Tyrosine Kinase Inhibitors Versus Chemotherapy in EGFR-Mutant Lung Cancer: A Meta-Analysis.

机构信息

Chee Khoon Lee, Pei Ni Ding, Sarah J. Lord, and Val Gebski, National Health and Medical Research Council Clinical Trials Centre, The University of Sydney; Chee Khoon Lee and Matthew Links, Cancer Care Centre, St George Hospital; Pei Ni Ding, Liverpool Hospital; Sarah J. Lord, School of Medicine, The University of Notre Dame; Nick Pavlakis, Royal North Shore Hospital, Sydney, Australia; Yi-Long Wu, Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangdong; Caicun Zhou, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China; Akira Inoue, Tohoku University Hospital, Sendai; Tetsuya Mitsudomi, Kinki University School of Medicine, Osaka-Sayama, Japan; Rafael Rosell, Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Barcelona, Spain; Richard J. Gralla, Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, NY; James Chih-Hsin Yang, Graduate Institute of Oncology, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan.

出版信息

J Clin Oncol. 2015 Jun 10;33(17):1958-65. doi: 10.1200/JCO.2014.58.1736. Epub 2015 Apr 20.

DOI:10.1200/JCO.2014.58.1736

PMID:25897154

Abstract

PURPOSE

We examined the impact of different epidermal growth factor receptor (EGFR) mutations and clinical characteristics on progression-free survival (PFS) in patients with advanced EGFR-mutated non-small-cell lung cancer treated with EGFR tyrosine kinase inhibitors (TKIs) as first-line therapy.

PATIENTS AND METHODS

This meta-analysis included randomized trials comparing EGFR TKIs with chemotherapy. We calculated hazard ratios (HRs) and 95% CIs for PFS for the trial population and prespecified subgroups and calculated pooled estimates of treatment efficacy using the fixed-effects inverse-variance-weighted method. All statistical tests were two sided.

RESULTS

In seven eligible trials (1,649 patients), EGFR TKIs, compared with chemotherapy, significantly prolonged PFS overall (HR, 0.37; 95% CI, 0.32 to 0.42) and in all subgroups. For tumors with exon 19 deletions, the benefit was 50% greater (HR, 0.24; 95% CI, 0.20 to 0.29) than for tumors with exon 21 L858R substitution (HR, 0.48; 95% CI, 0.39 to 0.58; Pinteraction < .001). Never-smokers had a 36% greater benefit (HR, 0.32; 95% CI, 0.27 to 0.37) than current or former smokers (HR, 0.50; 95% CI, 0.40 to 0.63; Pinteraction < .001). Women had a 27% greater benefit (HR, 0.33; 95% CI, 0.28 to 0.38) than men (HR, 0.45; 95% CI, 0.36 to 0.55; treatment-sex interaction P = .02). Performance status, age, ethnicity, and tumor histology did not significantly predict additional benefit from EGFR TKIs.

CONCLUSION

Although EGFR TKIs significantly prolonged PFS overall and in all subgroups, compared with chemotherapy, greater benefits were observed in those with exon 19 deletions, never-smokers, and women. These findings should enhance drug development and economic analyses, as well as the design and interpretation of clinical trials.

摘要

目的

我们研究了不同表皮生长因子受体（EGFR）突变和临床特征对接受 EGFR 酪氨酸激酶抑制剂（TKI）作为一线治疗的晚期 EGFR 突变非小细胞肺癌患者无进展生存期（PFS）的影响。

方法

本荟萃分析纳入了比较 EGFR TKI 与化疗的随机试验。我们计算了试验人群和预设亚组的 PFS 风险比（HR）和 95%置信区间（CI），并使用固定效应逆方差加权法计算了治疗效果的汇总估计值。所有统计检验均为双侧检验。

结果

在 7 项符合条件的试验（1649 例患者）中，与化疗相比，EGFR TKI 显著延长了总体 PFS（HR，0.37；95%CI，0.32 至 0.42）和所有亚组的 PFS。对于存在外显子 19 缺失的肿瘤，获益增加了 50%（HR，0.24；95%CI，0.20 至 0.29），而对于存在外显子 21 L858R 取代的肿瘤，获益增加了 48%（HR，0.48；95%CI，0.39 至 0.58；P 交互值<.001）。从不吸烟者的获益比当前或曾经吸烟者高 36%（HR，0.32；95%CI，0.27 至 0.37），而当前或曾经吸烟者的获益比从不吸烟者高 50%（HR，0.50；95%CI，0.40 至 0.63；P 交互值<.001）。女性的获益比男性高 27%（HR，0.33；95%CI，0.28 至 0.38），而男性的获益比女性高 45%（HR，0.45；95%CI，0.36 至 0.55；治疗-性别交互值 P =.02）。体能状态、年龄、种族和肿瘤组织学并不能显著预测 EGFR TKI 带来的额外获益。