Yu Jinyu, Wu Hanyu, Yang Lu, Liu Wei, Cao Baoshan, Liang Baosheng, Gu Yangchun
Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital, Beijing, PR China.
Department of Biostatistics, School of Public Health, Peking University, Beijing 100191, PR China.
Glob Med Genet. 2025 Jun 15;12(3):100064. doi: 10.1016/j.gmg.2025.100064. eCollection 2025 Sep.
It is a challenge for clinicians to choose the optimal third generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs) treatment for individual patients. In this meta-analysis we compare the efficacy of five third-generation EGFR-TKIs, as first-line and second-line therapies for non-small cell lung cancer (NSCLC) patients, and their adverse events (AEs).
A Bayesian hierarchical network meta-analysis was conducted to evaluate the hazard ratios (HR) of first-line therapeutic effects and AEs for these third-generation EGFR-TKIs comparing with first-generation EGFR-TKIs. Additionally, a simple comparison analysis was conducted to evaluate second-line therapeutic effects.
All third-generation TKIs exhibited superior efficacy compared to Gefitinib in first-line treatment. Furmonertinib achieved the lowest HR in the exon 19 deletions subgroup (HR: 0.35; 95 % CI: 0.23-0.54), while Lazertinib showed the most favorable HR in the exon 21 L858R subgroup (HR: 0.44; 95 % CI: 0.28-0.70) and among patients with brain metastases (HR: 0.33; 95 % CI 0.18-0.59). In the second-line setting, Furmonertinib achieved the highest numerically objective response rate across the overall population (74.0 %; 95 % CI: 68.0-80.0 %) and all evaluated subgroups. Adverse event analysis showed that Furmonertinib had the lowest overall AE incidence, and Lazertinib had the lowest rate of high-grade (≥ grade 3) AEs.
All third-generation EGFR-TKIs exhibited favorable efficacy in both first- and second-line settings. Differences in AE profiles were also noted.
为个体患者选择最佳的第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）治疗方案对临床医生来说是一项挑战。在这项荟萃分析中，我们比较了五种第三代EGFR-TKIs作为非小细胞肺癌（NSCLC）患者一线和二线治疗的疗效及其不良事件（AE）。
进行贝叶斯分层网络荟萃分析，以评估这些第三代EGFR-TKIs与第一代EGFR-TKIs相比一线治疗效果和AE的风险比（HR）。此外，进行了简单的比较分析以评估二线治疗效果。
在一线治疗中，所有第三代TKIs均显示出优于吉非替尼的疗效。伏美替尼在外显子19缺失亚组中HR最低（HR：0.35；95%CI：0.23-0.54），而拉泽替尼在外显子21 L858R亚组中（HR：0.44；95%CI：0.28-0.70）以及脑转移患者中（HR：0.33；95%CI 0.18-0.59）显示出最有利的HR。在二线治疗中，伏美替尼在总体人群（74.0%；95%CI：68.0-80.0%）和所有评估亚组中达到了最高的客观缓解率。不良事件分析表明，伏美替尼的总体AE发生率最低，而拉泽替尼的高级别（≥3级）AE发生率最低。
所有第三代EGFR-TKIs在一线和二线治疗中均显示出良好的疗效。AE谱也存在差异。
