Poor Prognosis With Coexistence Of EGFR T790M Mutation And Common EGFR-Activating Mutation In Non- Small Cell Lung Cancer

Abstract

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 workCorrespondence: Jianwei ShuaiDepartment of Physics, Xiamen University, Siming South Road 422-19, Xiamen 361005, People’s Republic of ChinaTel [phone]Email [email protected] ZhouDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital affiliated to Tongji University, 507 Zhengmin Road, Wu Jiao Chang, Yangpu, Shanghai 200433, People’s Republic of ChinaTel [phone]Email [email protected]: 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

Keywords

• pretreatment t790m mutation
• dual egfr mutations
• recurrence-free survival
• non-small cell lung cancer