Poor Prognosis With Coexistence Of EGFR T790M Mutation And Common EGFR-Activating Mutation In Non- Small Cell Lung Cancer
Authors Gao X, Zhao Y, Bao Y, Yin W, Liu L, Liu R, Yu Z, Zhou X, Shuai J
Received 22 May 2019
Accepted for publication 9 October 2019
Published 13 November 2019 Volume 2019:11 Pages 9621—9630
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Professor Lu-Zhe Sun
Xuejuan Gao,1,* Yanfeng Zhao,2,* Yi Bao,2,* Wei Yin,3 Liyu Liu,4 Ruchuan Liu,4 Zhengquan Yu,5 Xiao Zhou,2 Jianwei Shuai1,6
1Department of Physics, Xiamen University, Xiamen, People’s Republic of China; 2Department of Thoracic Surgery, Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai, People’s Republic of China; 3Key Laboratory of Oral Biomedical Engineering of Education, Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China; 4College of Physics, Chongqing University, Chongqing, People’s Republic of China; 5State Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, People’s Republic of China; 6State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, Xiamen University, Xiamen, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Jianwei Shuai
Department of Physics, Xiamen University, Siming South Road 422-19, Xiamen 361005, People’s Republic of China
Tel +86 13959287814
Department of Thoracic Surgery, Shanghai Pulmonary Hospital affiliated to Tongji University, 507 Zhengmin Road, Wu Jiao Chang, Yangpu, Shanghai 200433, People’s Republic of China
Tel +86 13916118590
Purpose: Previous studies have shown that the presence of EGFR T790M mutation may reduce the treatment efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung cancer. However, little is known about the clinical features and outcomes of EGFR T790M mutation in pretreated patients with NSCLC.
Patients and methods: The clinical features of EGFR-activating and T790M mutations were assessed in a large cohort of patients with EGFR-TKI-naïve NSCLC (all/EGFR mutations, n=16,347/7,687). The correlation between the pretreatment T790M mutation status and clinical outcomes was evaluated using univariate and multivariate analyses.
Results: Pretreatment T790M mutation was reported in 1.39% of the patients and coexisted with an EGFR-activating or uncommon mutation. The dual EGFR T790M and common EGFR-activating mutations were more likely to be detected in lung adenocarcinoma, whereas single T790M mutation was more prevalent in non-adenocarcinomas. The presence of de novo T790M mutation correlated with reduced recurrence-free survival (RFS) in patients with NSCLC (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.67–6.79, P = 0.001). After molecular stratification, T790M mutation was shown to exert adverse effects on the RFS of EGFR 19-del group (OR 2.89, 95% CI 1.10–7.91, P = 0.028) and EGFR L858R group (OR 3.43, 95% CI 1.33–8.88, P = 0.013). Furthermore, pretreatment T790M mutation promoted tumor metastasis to different sites.
Conclusion: T790M-positive tumors presented special clinical features, and the coexistence of T790M and common EGFR-activating mutations was associated with poor prognosis in patients with NSCLC.
Keywords: pretreatment T790M mutation, dual EGFR mutations, recurrence-free survival, non-small cell lung cancer
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]