携带罕见 EGFR 外显子 19 缺失-插入突变的患者对第一代 EGFR 抑制剂和奥希替尼治疗敏感，奥希替尼是在获得 T790M 后使用的。

Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M.

机构信息

Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Jianshe East Road 1, 450052, Zhengzhou, Henan, People's Republic of China.

Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, Jianshe East Road 1, 450052, Zhengzhou, Henan, People's Republic of China.

出版信息

BMC Cancer. 2021 Nov 13;21(1):1215. doi: 10.1186/s12885-021-08942-x.

BACKGROUND

In the existing next generation sequencing (NGS) system, epidermal growth factor receptor (EGFR) exon 19 deletion-insertion (19delins) is still interpreted into the category of EGFR exon 19 deletion (19del). However, the controversy exists whether the two mutation types have the similar responses and resistant mechanisms to first-generation EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) patients.

METHODS

We successively and retrospectively reviewed the NGS data of 3054 patients diagnosed as advanced NSCLC from November 2017 to September 2020. Finally, 41 patients with EGFR 19delins mutation and 41 patients with EGFR 19del mutation who received first-generation EGFR TKIs as first-line therapy were included in the study.

RESULTS

A total of 17 genotypes were identified in this study, including L747_P753delinsS (10/41), L747_A750delinsP (9/41), L747_T751delinsP (6/41) and E746_S752delinsV (3/41). Under the same baseline characteristics, the population of EGFR 19delins respond well to first line EGFR TKIs as well as those of EGFR 19del, with little difference in median progression-free survival (mPFS): 10.4 months vs. 13.1 months, p = 0.1076). Interestingly, patients with L747_T751delinsP seem to have a better mPFS than others (18.7 months vs. 13.1 months, p = 0.035). After the disease progression, both EGFR 19delins and EGFR 19del had similar rates of developing EGFR T790M mutation resistance (45.8% vs. 57.8%), and those receiving osimeritinib as second-line treatment obtain the similar survival benefits (mPFS: 12.0 months vs. 12.2 months (p = 0.97).

CONCLUSIONS

This retrospective cohort study furnish the evidence that therapeutic responses and survival of untreated NSCLC population with EGFR 19delins mutation are equal to those with common EGFR 19del mutation after administration of EGFR TKIs therapy.

背景

在现有的下一代测序（NGS）系统中，表皮生长因子受体（EGFR）外显子 19 缺失-插入（19delins）仍被解释为 EGFR 外显子 19 缺失（19del）。然而，在非小细胞肺癌（NSCLC）患者中，这两种突变类型对第一代 EGFR 酪氨酸激酶抑制剂（TKI）的反应和耐药机制是否相似仍存在争议。

方法

我们连续回顾性分析了 2017 年 11 月至 2020 年 9 月诊断为晚期 NSCLC 的 3054 例患者的 NGS 数据。最终，纳入 41 例 EGFR 19delins 突变和 41 例 EGFR 19del 突变接受第一代 EGFR TKI 作为一线治疗的患者。

结果

本研究共鉴定出 17 种基因型，包括 L747_P753delinsS（10/41）、L747_A750delinsP（9/41）、L747_T751delinsP（6/41）和 E746_S752delinsV（3/41）。在相同的基线特征下，EGFR 19delins 组的人群对一线 EGFR TKI 的反应与 EGFR 19del 组相似，中位无进展生存期（mPFS）差异无统计学意义：10.4 个月 vs. 13.1 个月，p=0.1076）。有趣的是，L747_T751delinsP 患者的 mPFS 似乎优于其他患者（18.7 个月 vs. 13.1 个月，p=0.035）。疾病进展后，EGFR 19delins 和 EGFR 19del 发生 EGFR T790M 耐药突变的比例相似（45.8% vs. 57.8%），二线接受奥希替尼治疗的患者获得相似的生存获益（mPFS：12.0 个月 vs. 12.2 个月，p=0.97）。