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