The Impact of Acquired EGFR T790M Mutation and 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 () T790M mutation, and the impact of circulating cell-free DNA (CfDNA) on overall survival for patients with advanced mutated adenocarcinoma resistant to first-line EGFR-tyrosine kinase inhibitor (TKI).

METHODS

A retrospective study was conducted to analyze -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 ( = 0.015). Liver metastasis (odds ratio [OR], 3.373; = 0.017) and other metastasis (OR, 3.063; = 0.023) were also independently correlated with T790M mutation incidence. T790M mutation was also associated with more than two progressive sites (OR, 3.382; = 0.006), liver progression (OR, 6.204; = 0.002), and bone progression (OR, 3.366; = 0.004). However, central nervous system progression was inversely correlated with T790M mutation (OR, 0.183; = 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 ( = 0.005).

CONCLUSION

Initial metastasis to the liver and other sites may be independent factors for secondary T790M mutation. T790M-positive lung adenocarcinoma has specific progression patterns. Moreover, not having CfDNA, being positive for Del19/L858R mutations, and being positive for T790M mutation have differing impacts on overall survival for patients with advanced -mutated adenocarcinoma resistant to first-line EGFR-TKI.