Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Lung Cancer. 2022 Aug;170:91-97. doi: 10.1016/j.lungcan.2022.06.006. Epub 2022 Jun 11.
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.
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.
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.
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.
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。
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。
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。
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。
