表皮生长因子受体 (EGFR) T790M 突变在血浆中的鉴定表明第一代酪氨酸激酶抑制剂治疗期间非小细胞肺癌进展中的失败部位，并预测临床预后：一项前瞻性观察研究。

Epidermal growth factor receptor (EGFR) T790M mutation identified in plasma indicates failure sites and predicts clinical prognosis in non-small cell lung cancer progression during first-generation tyrosine kinase inhibitor therapy: a prospective observational study.

机构信息

Center for Translational Medicine, Hangzhou First People's Hospital, Nanjing Medical University, No. 261 Huansha Road, Shangcheng District, Hangzhou, 310006, Zhejiang, China.

Department of Oncology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, 310006, Zhejiang, China.

出版信息

Cancer Commun (Lond). 2018 May 22;38(1):28. doi: 10.1186/s40880-018-0303-2.

DOI:10.1186/s40880-018-0303-2

PMID:29789021

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5993134/

Abstract

INTRODUCTION

Plasma circulating tumor DNA (ctDNA) is an ideal approach to detecting the epidermal growth factor receptor (EGFR) T790M mutation, which is a major mechanism of resistance to first-generation EGFR-tyrosine kinase inhibitor (TKI) therapy. The present study aimed to explore the association of ctDNA-identified T790M mutation with disease failure sites and clinical prognosis in non-small cell lung cancer (NSCLC) patients.

METHODS

Patients who progressed on first-generation TKIs were categorized into failure site groups of chest limited (CF), brain limited (BF) and other (OF). Amplification refractory mutation system (ARMS) and droplet digital PCR (ddPCR) were used to identify the T790M mutation in ctDNA. Prognosis was analyzed with Kaplan-Meier methods.

RESULTS

Overall concordance between the two methods was 78.3%. According to both ARMS and ddPCR, patients in the OF group had a significantly higher rate of T790M mutation than did patients in the BF and CF groups (P < 0.001), and a significantly higher T790M mutation rate was also observed in OF-group patients than in those in the CF and BF groups (P < 0.001). AZD9291 was found to be an excellent treatment option and yielded the longest survival for T790M+ patients in all groups who had progressed on EGFR-TKIs; for other treatments, the prognosis of T790M- patient subgroups varied.

CONCLUSIONS

The present study demonstrates that T790M mutation in ctDNA is associated with failure sites for NSCLC patients after EGFR-TKI therapy and indicates that both failure site and T790M mutational status greatly influence treatment selection and prognosis.

摘要

简介

血浆循环肿瘤 DNA（ctDNA）是检测表皮生长因子受体（EGFR）T790M 突变的理想方法，这是第一代 EGFR-酪氨酸激酶抑制剂（TKI）治疗耐药的主要机制。本研究旨在探讨非小细胞肺癌（NSCLC）患者 ctDNA 鉴定的 T790M 突变与疾病失败部位和临床预后的关系。

方法

将第一代 TKI 治疗进展的患者分为胸部局限性（CF）、脑局限性（BF）和其他（OF）失败部位组。扩增受阻突变系统（ARMS）和液滴数字 PCR（ddPCR）用于鉴定 ctDNA 中的 T790M 突变。采用 Kaplan-Meier 方法分析预后。

结果

两种方法的总体一致性为 78.3%。根据 ARMS 和 ddPCR，OF 组患者 T790M 突变率明显高于 BF 组和 CF 组（P<0.001），OF 组患者 T790M 突变率也明显高于 CF 组和 BF 组（P<0.001）。AZD9291 被发现是一种极好的治疗选择，在所有进展后的 EGFR-TKI 治疗的 NSCLC 患者中，T790M+患者的生存时间最长；对于其他治疗方法，T790M-患者亚组的预后各不相同。