Clinical Utility of Liquid Biopsy for EGFR Driver, T790M Mutation and EGFR Amplification in Plasma in Patients with Aacquired Resistance to Afatinib

Abstract

Background: Cell-free DNA (cfDNA) genotyping in plasma using the cobas EGFR Mutation Test v2 (cobas) is the first liquid biopsy as a companion diagnosis to identify the EGFR T790M mutation (T790M) after the failure of treatment of EGFR-tyrosine kinase inhibitor (TKI) (1st generation, gefitinib [G] and erlotinib [E] and afatinib [A]). This study investigated the clinical utility of a liquid biopsy for patients who acquired resistance to afatinib.Methods: We prospectively collected plasma from 51 patients who had acquired resistance to afatinib between April 2015 and November 2016 to evaluate the frequency of T790M using the cobas and digital droplet PCR (UMIN000025112). Additionally, we retrospectively reviewed 38 patients who tested by cobas in plasma after G/E failure to compare for T790M detection between A and with G/E.Results: The detection rate of EGFR sensitive mutation (EGFR sens.) and T790M in plasma in patients treated with A (A group) as an initial EGFR-TKI was lower than with G/E followed by A (G/E→A), although the differences were not significant (EGFR sens.: 41% (A) vs. 67% (G/E→A), P=0.1867; and T790M: 8% (A) vs. 17% (G/E→A), P=0.5798). In first-line setting, the detection rate for EGFR-sens. and T790M in plasma by cobas was lower in A group than in G/E group, although there was no significant difference (EGFR sens.: 34% (A) vs. 52% (G/E), P=0.2072; and T790M: 10% (A) vs. 27% (G/E), P=0.1161).Conclusion: The detection of EGFR sens. and T790M in plasma by cobas might be insufficient in patients treated with afatinib than with G/E.