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T. Yoshida

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    Poster Session (ID 8)

    • Event: ACLC 2018
    • Type: Poster Session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 11/07/2018, 00:00 - 00:00, Poster Hall
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      P072 - Low Detection Rate of EGFR Driver and T790M Mutation in Plasma by (ID 110)

      00:00 - 00:00  |  Author(s): T. Yoshida

      • Abstract

      Cell free DNA (cfDNA) genotyping in plasma by cobas EGFR Mutation Test v2 (cobas test) is the first liquid biopsy approved as companion diagnostic systemtest to identify patients with EGFR T790M (T790M) mutation after first-generation EGFR-TKIs (G: gefitinib and erlotinib: E)and second-generation EGFR-TKIs (afatinib) failure. However, it remains unclear whether cobas testin plasma is sufficient method for detecting T790M mutation after afatinib failure. This study aimed atinvestigating the efficacy and sensitivity of cfDNA genotyping in plasma by cobas test for detecting T790M after the resistance to afatinib.

      We collected plasma in patients who acquired resistance to afatinib between November 2016 and April 2018 as multi-institutional prospective observational study (UMIN000025112). All plasma samples were assessed by cobas test. Additionally, we retrospectively reviewed patients who had underwent cobas test in plasma after resistance to G/E as control arm. In all patients, patient characteristics, efficacy of EGFR-TKIs, and T790M status in plasma and tissue were reviewed.

      Fifty-one patients with resistance to afatinib were enrolled in the prospective observation study. Of these patients, 35 patients were treated with afatinib as first-line setting. Fourteen patients (40%) had EGFR driver mutation in plasma, and only 3 patients (7.3%) had T790M in plasma.To compare the detection rate of EGFR driver and T790M mutation in plasma between patients treated with G/E than with afatinib, we selected 38 patients who were treated G/E as first-line setting and underwent plasma assay after resistance to G/E. There was no difference in the detection of EGFR driver mutation and T790M mutation in patients treated with G/E than afatinib ([EGFR driver mutation]: 52.6% vs 40.0%, p=0.28 and [T790M]: 23.7% vs. 8.6%, p=0.08). However, on patients with EGFR driver mutation positive in plasma (N=34), the T790M detection in plasma was significantly higher in patients treated with G/E than those with afatinib (45.0% vs. 14.3%, p=0.05). On the other hands, in 42 patients who underwent tissue analysis for T790M mutation, there was no significant difference in the frequency of T790M mutation in tissue by rebiopsy between two groups (G/E vs afatinib: 20.7% vs 23.7%, p=0.77).

      CfDNA analysis for T790M mutation by cobas test in patients treated with afatinib could be insufficient compared with those with first-generation EGFR-TKIs (G and E).