EGFR Mutations in Cell-free Plasma DNA from Patients with Advanced Lung Adenocarcinoma: Improved Detection by Droplet Digital PCR

BACKGROUND: Analysis of cell-free DNA from blood could provide an alternative method for identifying genomic changes in the tumors of patients with advanced lung adenocarcinoma. OBJECTIVE: We compared the performance of droplet digital PCR (ddPCR) and Cobas(®) EGFR Mutation Test v2 (Cobas) for detecting EGFR mutations in cell-free plasma DNA. PATIENTS AND METHODS: Plasma samples from patients with advanced EGFR-mutated lung adenocarcinoma were analyzed for EGFR T790M, exon 19 deletions, and L858R mutations by both ddPCR and Cobas. RESULTS: T790M testing was performed in 354 plasma samples collected from 129 patients. The concordance rate between ddPCR and Cobas for T790M, sensitivity, and specificity were 86, 100, and 85%, respectively. Exon 19 deletions were analyzed in 196 plasma samples obtained from 71 of the 129 patients using both platforms. The concordance rate between ddPCR and Cobas for exon 19 deletions, sensitivity, and specificity were 90, 92, and 89%, respectively. L858R mutations were studied in 124 plasma samples obtained from 44 of the 129 patients using both assays. The concordance rate between ddPCR and Cobas for L858R, sensitivity, and specificity were 90, 91, and 89%, respectively. In patients who progressed under treatment with an EGFR TKI (n = 50), the T790M positivity rate was 66% using ddPCR, but only 24% using Cobas. CONCLUSIONS: We observed a high concordance between ddPCR and Cobas in detecting EGFR mutations in plasma samples of patients with advanced EGFR-mutated lung adenocarcinoma, but ddPCR was more sensitive than Cobas.