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Aleksander Barinow-Wojewodzki



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    P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.13-14 - The Clinical Usefulness of Liquid Biopsy for Detection and Dynamic Monitoring of EGFR T790M in NSCLC Patients on EGFR-TKI Therapy (ID 14135)

      16:45 - 18:00  |  Author(s): Aleksander Barinow-Wojewodzki

      • Abstract
      • Slides

      Background

      The greatest limitation of the I & II generation EGFR TKIs’ efficacy is the resistance acquired by most treated patients through the T790M mutation present in exon 20 of EGFR gene. Non-invasive access to the tumor DNA circulating in the blood of NSCLC patients, so called liquid biopsy, enables the real-time monitoring of status and level of mutated EGFR gene DNA (mEGFR) during EGFR TKI treatment instead of retrospective evaluation of tumor tissue specimens. In the present study we evaluated the feasibility and the diagnostic usefulness of quantitative EGFR mutations analysis in liquid biopsy collected from NSCLC patients during EGFR TKI treatment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The study group consists of 40 patients with advanced NSCLC treated with EGFR TKI (erlotinib, gefitinib or afatinib) in the first line. Peripheral blood is prospectively collected at the time of diagnosis (baseline) and then every month during treatment. In 10 patients (7 patients with deletion in exon 19 and 3 patients with L858R mutation in exon 21 of EGFR gene) sampling was followed until clinical progression. The mutated EGFR DNA was analyzed quantitively in plasma using cobas EGFR Mutation Test v2 (Roche, Germany).

      4c3880bb027f159e801041b1021e88e8 Result

      The mEGFR in plasma of NSCLC patients demonstrated notable dynamics during EGFR TKI treatment. In 8 out of 10 (80%) patients followed until progression, who responded well to EGFR TKIs, the complete clearence of mEGFR in plasma in first 2 months of treatment was observed, regardless the type of activating EGFR mutation. The levels of mEGFR remained undetectable in plasma for several months of treatment in those patients. In 6 (60%) patients a rapid raise to or above mEGFR baseline preceded clinical progression in time, in 4 patients by at least four weeks. In 4 patients, the raising level of mEGFR in plasma was accompanied by the increasing T790M mutation level. In 2 patients, the plasma level of mEGFR was undetectable at diagnosis and during treatment.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The dynamic changes in levels of mutated EGFR gene DNA in plasma of NSCLC patients reflect their response to EGFR TKI treatment. The monitoring of T790M mutation levels in plasma by allele-specific qPCR assay allows to observe disease progression on EGFR TKIs much earlier than conventional imaging techniques. The study is ongoing: at least 80 patients are to be recruited and clinical data correlated with results of molecular tests. This study is financed by the investigator initiated research grant from AstraZeneca.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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