探究真实世界中表皮生长因子受体(EGFR)敏感突变的晚期NSCLC患者使用吉非替尼、厄洛替尼、埃克替尼一线治疗进展后T790M突变的分布特征。

2017年6月至2019年6月期间557例肺癌患者，145例经病理组织学或细胞学确诊为晚期非小细胞肺癌(NSCLC)且具有EGFR敏感突变的患者，给予吉非替尼、厄洛替尼、埃克替尼一线治疗。随访进展后，采集其外周血10 ml，利用Super-ARMS法检测T790M突变。通过χ²检验，Kaplan-Meier分析，回顾性分析晚期NSCLC患者接受吉非替尼、厄洛替尼、埃克替尼一线治疗后T790M突变患者的分布特征。

回顾性分析的145例患者，56例一线接受吉非替尼治疗，16例接受厄洛替尼治疗，73例接受埃克替尼治疗。Super-ARMS检测结果显示，一代EGFR-TKIs治疗进展后T790M突变的总体发生率为40% (58/145)，其中吉非替尼组41.07% (23/56)、厄洛替尼组31.25%(5/16)、埃克替尼组41.10% (30/73)。三组患者之间T790M突变的发生率无统计学差异。但是，肺腺癌(P＝0.0001)及初始EGFR突变为19del(P＝0.0014)的患者更易发生T790M突变。T790M阳性患者中，吉非替尼、厄洛替尼、埃克替尼的中位PFS(mPFS)分别为：11个月、18个月和12个月，组间无统计学差异。TKI治疗1年、2年后T790M突变率及T790M阳性人群的中位PFS均无统计学差异。

真实世界中吉非替尼、厄洛替尼、埃克替尼一线治疗晚期NSCLC耐药进展后，其血检标本T790M的突变发生率无统计学差异。但是，初始突变为19del的患者相较于L858R突变的患者更容易发生T790M突变。这也进一步预示着NSCLC患者精细化管理的必要性。

The purpose of this study is to study the distribution characteristics of T790M mutations in advanced NSCLC patients with epidermal growth factor receptor (EGFR)-sensitive mutations in the real world after receiving first-line treatment with three different generations of EGFR-TKIs.

Between June 2017 and June 2019, a total of 557 patients with NSCLC were enrolled in this study. 145 patients with advanced non-small cell lung cancer (NSCLC) diagnosed with histopathology or cytology with EGFR-sensitive mutations were randomized to gefitinib, erlotinib, icotinib first-line treatment. By χ² test, Kaplan-Meier method, retrospectively analyze the probability of acquiring T790M after taking first-line TKIs (gefitinib, Erlotinib, icotinib) and clinical features of patients with T790M mutation.

Of the 557 patients screened, 145 fulfilled the inclusion criteria and were enrolled in this retrospective analysis. In these patients, 56 patients received gefitinib in the first line, 16 received erlotinib, and 73 received icotinib. Super-ARMS test results showed that the overall incidence of T790M mutation was 40% (58/145), including 41.07% (23/56) in the gefitinib group and 31.25 in the erlotinib group % (5/16), 41.10% (30/73) in the icotinib group. There was no statistical difference in the incidence of T790M mutation among the three groups. However, patients with lung adenocarcinoma (P=0.0001) and patients with an initial EGFR mutation of 19del (P=0.0014) had a higher frequency of T790M mutations. Among the T790M positive population, the median PFS of gefitinib, erlotinib and ectinib was: 11, 18 and 12 m. The 1-year and 2-year detection rates of T790M mutation were 6.25%, 29.09%, 24.66% and 31.24, 45.45% and 41.09%, no statistical difference between the groups.

There was no significant difference in the incidence of T790M mutation among the advanced NSCLC treatment with first-generation EGFR-TKI. In the T790M positive population, the median PFS and the 1-year and 2-year detection rates of T790M mutation were no statistical difference between the groups. This further indicates the necessity of refined management of NSCLC patients.