A Higher Proportion of the EGFR T790M Mutation May Contribute to the Better Survival of Patients with Exon 19 Deletions Compared with Those with L858R

被引：85

作者：

Ke, E-E ^{[1
,2
,3
]}

Zhou, Qing ^{[2
,3
]}

Zhang, Qiu-Yi ^{[4
,5
,6
]}

Su, Jian ^{[2
,3
]}

Chen, Zhi-Hong ^{[2
,3
]}

Zhang, Xu-Chao ^{[2
,3
]}

Xu, Chong-Rui ^{[2
,3
]}

Yang, Jin-Ji ^{[2
,3
]}

Tu, Hai-Yan ^{[2
,3
]}

Yan, Hong-Hong ^{[2
,3
]}

Zhang, Yi-Chen ^{[2
,3
]}

Niu, Fei-Yu ^{[2
,3
]}

Wu, Yi-Long ^{[2
,3
]}

机构：

[1] Southern Med Univ, Guangzhou, Guangdong, Peoples R China

[2] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China

[3] Guangdong Acad Med Sci, Guangzhou, Guangdong, Peoples R China

[4] Chinese Acad Med Sci, Natl Canc Ctr, Canc Hosp, Shenzhen, Peoples R China

[5] Chinese Acad Med Sci, Shenzhen Hosp, Shenzhen, Peoples R China

[6] Peking Union Med Coll, Shenzhen, Peoples R China

来源：

JOURNAL OF THORACIC ONCOLOGY | 2017年 / 12卷 / 09期

基金：

中国国家自然科学基金;

关键词：

T790M mutation; Exon; 19; deletions; L858R mutation; Resistance mechanisms; CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; OPEN-LABEL; GEFITINIB; OSIMERTINIB; CHEMOTHERAPY; SENSITIVITY; AFATINIB;

D O I：

10.1016/j.jtho.2017.05.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: Increasing evidence has demonstrated that exon 19 deletions (Del19) and L858R mutation in EGFR have different prognostic and predictive roles in NSCLC. We aimed to investigate whether these two mutations produced differences in mechanisms of resistance to EGFR tyrosine kinase inhibitors. Methods: Consecutive patients with advanced EGFR-mutant NSCLC who acquired resistance to EGFR tyrosine kinase inhibitors and underwent postprogression biopsy were enrolled. Mechanisms including T790M mutation, mesenchymalepithelial transition proto-oncogene (MET) amplification, and histological transformation, as well as KRAS, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) mutation, and anaplastic lymphoma receptor tyrosine kinase gene (ALK) fusion, were analyzed. Results: The prevalence of T790M mutation was significantly higher in the Del19 subgroup than that in L858R subgroup (50.4% versus 36.5%, p = 0.043). Apart from this, there was no difference in other mechanisms including MET amplification and histological transformation. The median overall survival (OS) of patients with T790M mutation was 36.0 months (95% confidence interval [CI]: 30.9-41.2), which was significantly longer than the 26.5 months (95% CI: 24.0-29.0) in MET-positive patients, 19.7 months (95% CI: 18.2-21.2) in patients with histological transformation, and 23.0 months (95% CI: 17.4-28.6) in the KRAS/PIK3CA/ALK-altered population (p = 0.021). The hazard ratios of the MET-amplification subgroup and subgroup with histological transformation were 1.809-fold and 2.370-fold higher than that in T790M-positive subgroup. The median OS times were months 33.3 (95% CI: 28.9-37.7) in the De119 subgroup and 26.4 months (95% CI: 23.2-29.6) in the L858R subgroup (p = 0.028). However, in multivariable analysis adjusted for T790M genotype, the EGFR mutation subtype was no longer found to be significant. Conclusions: Significant OS benefit was observed in patients with T790M mutation, suggesting that a larger proportion of T790M mutation might contribute to the better survival of patients with Del19. (C) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

引用

页码：1368 / 1375

页数：8