Background

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.

Objective

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.

Patients and Methods

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.

Results

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%).

Conclusions

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.

中文翻译：

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对具有不同EGFR外显子19突变的非小细胞肺癌中第一代酪氨酸激酶抑制剂的异质反应。

背景

表皮生长因子受体（EGFR）外显子19缺失（19dels）出现在许多变体中，尽管缺失和插入位置有所不同，但在先前发表的试验中并未加以区分。

目的

这项研究的目的是研究具有不同EGFR外显子19dels的患者对第一代酪氨酸激酶抑制剂（TKIs）的治疗反应，以及他们的肿瘤对这些TKIs产生耐药性的机制。

患者和方法

回顾性分析了2011年7月至2019年6月之间195名携带EGFR外显子19dels并接受第一代EGFR TKI的患者的临床结局。

结果

总共鉴定出二十个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）。两组之间接受EGFR TKIs治疗的患者的中位无进展生存期（PFS）显着不同（p  <0.001）。从T751或S752开始携带EGFR外显子19dels的患者中位PFS最短（2.9个月），其次是E746（11.4个月）和L747（17.2个月）。分析140例治疗进展的患者，从T751或S752开始的EGFR外显子19dels与T790M突变的发生率低（16.7％）相关。

结论

删除位置和类型变异（有或没有插入和/或取代）可能会影响第一代TKI疗效，在决定应使用哪种EGFR TKI时应考虑不同的EGFR外显子19del。