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Eun Young Kim



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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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      P2.13-12 - The deNovo T790M Mutation Recovered by ddPCR is Associated with a Poor Response to 1st and 2nd Generation EGFR-TKI in Lung Adenocarcinoma. (ID 13541)

      16:45 - 18:00  |  Author(s): Eun Young Kim

      • Abstract
      • Slides

      Background

      The discovery of the EGFR-tyrosine kinase inhibitor (TKI) sensitizing mutation and the customized application of the 1st generation EGFR-TKI dramatically improved the clinical outcome of patients with lung adenocarcinoma. However, EGFR-mutation positive lung adenocarcinoma has ultimately acquired drug resistance against EGFR-TKI, resulting in treatment failure. The EGFR T790M mutation is found in approximately half of patients with resistance during 1st and 2nd generation EGFR-TKI therapy and is also a therapeutic biomarker of indications for EMSI treatment. In this study, authors aimed to investigate the effect of presence of T790M mutation in the treatment naïve lung adenocarcinoma tissues on the response to 1st and 2nd generation EGFR-TKI using droplet digital PCR (ddPCR).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      113 specimens from the patients who visited Severance Hospital from 2009 to 2017 were recruited from the institutional tissue bank. Detailed inclusion criteria for the cases are as follows; (1) pathologically proven lung adenocarcinoma; (2) pStage IIIB ~ IV (3) 1st line treatment with 1st or 2nd generation EGFR-TKI (4) sufficient FFPE tissue blocks for gDNA extraction (5) provided informed consent for the use of tissues. gDNA was extracted with QIAamp DNA FFPE tissue kit and T790M mutation was identified using BioRad Droplet Digital PCR (ddPCR) QX200 according to the manufacturer's manual.

      4c3880bb027f159e801041b1021e88e8 Result

      To date, 46 cases have been tested for T790M mutations, with 69.2% cases with ≥10 copies, 42.3% with 20 copies, and 30.7% with ≥30 copies. When 30 copies or more were defined as positive, the cases with higher de novo T790M mutations showed shorter progression free survival for 1st and 2nd generation EGFR-TKI. In 31 cases, EGFR mutation was measured at re-biopsy. There was no significant relationship between pre-treatment T790M mutation status and re-biopsy T790M mutation, and there was no significant relationship between pre-treatment and overall survival.

      *Depending on the results of additional experiments, the above information will be updated at the time of presentation.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In treatment naïve lung adenocarcinoma, a de novo T790M mutation is frequently observed and may related to the poor response to 1st and 2nd generation EGFR-TKI. The further studies on the applicability of EMSI to these subgroups and its clinical usefulness are required.

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