The Impact of Acquired EGFR T790M Mutation and EGFR Circulating Cell-Free DNA on Survival in Patients with Lung Adenocarcinoma Following EGFR-TKI Therapy

OBJECTIVE: To utilize liquid biopsy to investigate the potential clinical factors influencing the incidence of the acquired epidermal growth factor receptor (EGFR) T790M mutation, and the impact of EGFR circulating cell-free DNA (CfDNA) on overall survival for patients with advanced EGFR-mutated adenocarcinoma resistant to first-line EGFR-tyrosine kinase inhibitor (TKI). METHODS: A retrospective study was conducted to analyze EGFR-mutated stage IIIB-IV adenocarcinoma patients who received an EGFR-TKI (gefitinib, erlotinib, or afatinib) as first-line therapy and then underwent a liquid biopsy exam at disease progression. RESULTS: A total of 135 patients were included, and the T790M mutation was detected in 51 patients (37.7%). The incidence of T790M mutation increased with the number of initial metastatic sites (p = 0.015). Liver metastasis (odds ratio [OR], 3.373; p = 0.017) and other metastasis (OR, 3.063; p = 0.023) were also independently correlated with T790M mutation incidence. T790M mutation was also associated with more than two progressive sites (OR, 3.382; p = 0.006), liver progression (OR, 6.204; p = 0.002), and bone progression (OR, 3.366; p = 0.004). However, central nervous system progression was inversely correlated with T790M mutation (OR, 0.183; p = 0.027). Overall survival was the longest among the patients without CfDNA, followed by those shedding T790M mutation and those shedding Del 19/L858R mutations (p = 0.005). CONCLUSION: Initial metastasis to the liver and other sites may be independent factors for secondary EGFR T790M mutation. T790M-positive lung adenocarcinoma has specific progression patterns. Moreover, not having EGFR CfDNA, being positive for Del19/L858R mutations, and being positive for T790M mutation have differing impacts on overall survival for patients with advanced EGFR-mutated adenocarcinoma resistant to first-line EGFR-TKI.