吸烟习惯对晚期 EGFR 突变型 NSCLC 中 EGFR-TKI 联合抗血管生成药物疗效的影响。
Effect of smoking habits on the efficacy of EGFR-TKI plus anti-angiogenic agent in advanced EGFR-mutant NSCLC.
机构信息
Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
出版信息
Lung Cancer. 2022 Aug;170:91-97. doi: 10.1016/j.lungcan.2022.06.006. Epub 2022 Jun 11.
BACKGROUND
The types of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients who could obtain significant clinical benefit from the dual inhibition of EGFR/vascular EGFR (VEGFR) pathways remain unclear. No consensus has been reached on the significance of smoking habits in clinical benefit obtained from EGFR-TKI plus anti-angiogenic agents.
METHODS
PubMed, EMBASE, and Cochrane databases for all phase II/III randomized clinical trials (RCTs) investigating the efficacy of EGFR-TKI combined with anti-angiogenic agents stratified by smoking habits (updated October 2021) were searched systematically. The primary outcomes were the pooled HRs for PFS/OS in smokers and non-smokers, and differences in efficacy of EGFR-TKI plus anti-angiogenic treatment between smokers and non-smokers, measured by difference in PFS and OS.
RESULTS
Seven phase II/III RCTs involving 1452 patients were identified. The pooled analysis demonstrated that EGFR-TKI plus anti-angiogenic agent could decrease the risk of progression by 40% (HR, 0.60; 95%CI 0.48-0.75) in smokers when compared with EGFR-TKI alone, but not in non-smokers (HR, 0.92; 95%CI 0.68-1.25). The comparison analysis further demonstrated that EGFR-mutated NSCLC patients who smoked obtained greater progression-free survival (PFS) benefit from treatment with EGFR-TKI plus anti-angiogenic agents (HR, 0.68; 95%CI 0.51-0.91). Consistent with the results for PFS, smokers receiving EGFR-TKI plus anti-angiogenic agents appeared to exhibit better overall survival (OS) than non-smokers but not to a statistically significant degree (HR, 0.60; 95%CI 0.23-1.52). Meta-regression analysis revealed no significant effect of the line of treatment (P = 0.52), trial phase (P = 0.52), EGFR-TKI type (P = 0.13), or anti-angiogenic agent type (P = 0.50) on PFS effect sizes under multivariate models.
CONCLUSION
Comprehensive analysis suggested that EGFR-TKI plus anti-angiogenic agents led to favorable PFS among smoking EGFR-mutant patients, comparable to nonsmokers, which might provide a useful guide for clinicians.
背景
表皮生长因子受体（EGFR）-突变非小细胞肺癌（NSCLC）患者通过双重抑制 EGFR/血管内皮生长因子受体（VEGFR）途径获得显著临床获益的类型仍不清楚。吸烟习惯对 EGFR-TKI 联合抗血管生成药物获得的临床获益的意义尚无共识。
方法
系统检索 PubMed、EMBASE 和 Cochrane 数据库中所有按吸烟习惯分层的 EGFR-TKI 联合抗血管生成药物治疗的 II/III 期随机临床试验（RCT）的相关数据（更新于 2021 年 10 月）。主要结局为吸烟者和不吸烟者的无进展生存期（PFS）/总生存期（OS）的合并 HR，以及吸烟者和不吸烟者之间 EGFR-TKI 联合抗血管生成治疗疗效的差异，通过 PFS 和 OS 的差异来衡量。
结果
共纳入 7 项涉及 1452 例患者的 II/III 期 RCT。汇总分析表明，与 EGFR-TKI 单药治疗相比，EGFR-TKI 联合抗血管生成药物可使吸烟者疾病进展风险降低 40%（HR，0.60；95%CI，0.48-0.75），但在不吸烟者中则无此作用（HR，0.92；95%CI，0.68-1.25）。比较分析进一步表明，吸烟的 EGFR 突变型 NSCLC 患者从 EGFR-TKI 联合抗血管生成药物治疗中获得了更长的无进展生存期（PFS）获益（HR，0.68；95%CI，0.51-0.91）。与 PFS 的结果一致，接受 EGFR-TKI 联合抗血管生成药物治疗的吸烟者的总生存期（OS）似乎优于不吸烟者，但无统计学意义（HR，0.60；95%CI，0.23-1.52）。Meta 回归分析显示，在多变量模型中，治疗线数（P=0.52）、试验阶段（P=0.52）、EGFR-TKI 类型（P=0.13）和抗血管生成药物类型（P=0.50）对 PFS 效应大小均无显著影响。
结论
综合分析表明，EGFR-TKI 联合抗血管生成药物在吸烟的 EGFR 突变型患者中可带来有利的 PFS，与不吸烟者相当，这可能为临床医生提供有用的指导。
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