Abstract
BackgroundCell-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 inhibitors (TKIs) (1st generation, gefitinib [G] and erlotinib [E] and 2nd generation, afatinib [A]). This study investigated the clinical utility of a liquid biopsy for patients who acquired resistance to afatinib.MethodsWe prospectively collected plasma from 51 patients who had acquired resistance to afatinib between April 2015 and November 2016 to evaluate the frequency of T790M by 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.ResultsThe detection rate of EGFR-driver and T790M in plasma in patients treated with A (A group) as a first-line EGFR-TKI was lower than with G/E followed by A (G/E→A group), although the differences were not significant (EGFR-driver: 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-driver and T790M in plasma by cobas was lower in A group than in G/E group, although there was no significant difference (EGFR-driver: 34% [A] vs. 52% [G/E], P=0.2072; and T790M: 10% [A] vs. 27% [G/E], P=0.1161).ConclusionThe detection of EGFR-driver and T790M in plasma by cobas in patients treated with afatinib might be lower than with G/E in a real-world setting.
Highlights
Cell-free DNA genotyping in plasma using the cobas Epidermal growth factor receptor (EGFR) Mutation Test v2 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 inhibitors (TKIs) (1st generation, gefitinib [G] and erlotinib [E] and 2nd generation, afatinib [A])
To evaluate the difference in the detection of EGFR-driver and T790M mutation in plasma from patients treated with first-generation EGFR-TKIs (G/E) and afatinib as initia EGFR-TKIs, we retrospectively collected data on 33 patients who had been treated with G/ E as first-line EGFR-TKIs setting, and whose plasma samples had been analyzed using the cobas test to evaluate the presence of T790M mutation; these patients were regarded as a control arm (Fig. 1b)
Detection rate of EGFR driver and T790M mutation between Gefitinib/Erlotinib and Afatinib groups we evaluated whether the types of EGFR-TKIs (G/ E or afatinib) as first-line EGFR-TKI affected the detection of EGFR driver and T790M mutations in plasma
Summary
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 inhibitors (TKIs) (1st generation, gefitinib [G] and erlotinib [E] and 2nd generation, afatinib [A]). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has prolonged progression-free survival (PFS) compared with platinum-doublet chemotherapy as initial systemic therapy, and have been a standard firstline therapy for patients with EGFR mutations [1,2,3]. The emergence of the EGFR T790M point mutation is the most common mechanism of acquired resistance to the EGFR-TKIs gefitinib, erlotinib and afatinib [6, 7]. EGFR wild-type amplification has been reported as a mechanism or resistance to EGFR-TKIs, including osimertinib [9, 10]
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