Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
Target Oncol. 2020 Jun;15(3):357-364. doi: 10.1007/s11523-020-00722-0.
Epidermal growth factor receptor (EGFR) exon 19 deletions (19dels) appear in a large number of variants, which has not been distinguished in previously published trials despite differences in deletion and insertion locations.
The aim of this study was to investigate the therapeutic response of patients with different EGFR exon 19dels to first-generation tyrosine kinase inhibitors (TKIs) and the mechanisms by which their tumors acquire resistance to these TKIs.
The clinical outcomes of 195 patients harboring EGFR exon 19dels and receiving first-generation EGFR TKIs between July 2011 and June 2019 were retrospectively analyzed.
A total of twenty EGFR exon 19dels variants were identified. The patients were divided into three groups according to the first residue of the deletion, including E746, L747, and other residues (T751 or S752). The median progression-free survival (PFS) of patients treated with EGFR TKIs was significantly different between groups (p < 0.001). Patients harboring EGFR exon 19dels starting at T751 or S752 had the shortest median PFS (2.9 months), followed by those with E746 (11.4 months) and those with L747 (17.2 months). Analyzing 140 patients who had progressed on therapy, EGFR exon 19dels beginning at T751 or S752 were associated with a low incidence of the T790M mutation (16.7%).
Deletion location and type variants (with or without an insertion and/or a substitution) might affect first-generation TKI efficacy, and different EGFR exon 19dels should be considered when making decisions on which EGFR TKI should be used.
表皮生长因子受体（EGFR）外显子 19 缺失（19dels）在大量变体中出现，尽管缺失和插入位置不同，但在之前发表的试验中并未区分。
本研究旨在探讨不同 EGFR 外显子 19dels 患者对第一代酪氨酸激酶抑制剂（TKIs）的治疗反应，以及肿瘤对这些 TKI 产生耐药性的机制。
回顾性分析了 2011 年 7 月至 2019 年 6 月期间接受第一代 EGFR TKI 治疗的 195 例携带 EGFR 外显子 19dels 的患者的临床结局。
共确定了 20 种 EGFR 外显子 19dels 变体。根据缺失的第一个残基，将患者分为三组，包括 E746、L747 和其他残基（T751 或 S752）。接受 EGFR TKI 治疗的患者中位无进展生存期（PFS）在组间差异有统计学意义（p<0.001）。以 T751 或 S752 起始的 EGFR 外显子 19dels 患者的中位 PFS 最短（2.9 个月），其次是 E746 起始的患者（11.4 个月）和 L747 起始的患者（17.2 个月）。对 140 例治疗进展的患者进行分析，以 T751 或 S752 起始的 EGFR 外显子 19dels 与 T790M 突变的发生率较低（16.7%）相关。
缺失位置和类型变异（有无插入和/或取代）可能影响第一代 TKI 的疗效，在决定使用哪种 EGFR TKI 时应考虑不同的 EGFR 外显子 19dels。
