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Hongmei Zhang



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    Mini Oral session I (ID 60)

    • Event: ELCC 2019
    • Type: Mini Oral session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 08:00 - 08:50, Room A
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      114O - Potential resistance mechanisms using next generation sequencing from Chinese EGFR T790M+ non-small cell lung cancer patients with primary resistance to osimertinib: A multicenter study (ID 157)

      08:00 - 08:50  |  Author(s): Hongmei Zhang

      • Abstract
      • Presentation
      • Slides

      Background

      Osimertinib (AZD9291) is a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated significant clinical benefits in patients with EGFR sensitizing mutations or T790M mutation. However, approximately 5% to 15% of patients with non-small-cell lung cancer (NSCLC) with EGFR T790M mutation has primary resistance to osimertinib treatment. The underlying mechanism is unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      A total of 117 patients with stage IIIb-IV EGFR-T790M NSCLC were undergoing tumor biopsies or blood withdrawing by the time of primary or acquiring to osimertinib, including FFPE samples, serum samples and serous effusions. We used targeted NGS to detect genes status of patients.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      Among 117 patients treated with osimertinib, 82.91% (97/117) developed acquired resistance, and 7.69% (9/117) had primary resistance. Using the specimens at the baseline, there were 3 (33.33%) patients with MET amplification, 1 (11.11%) patient with BCL2L11 loss (BIM deletion polymorphism), 1 (11.11%) patient with ERBB2 amplification, 1 (11.11%) patient with PTEN mutation, 1 (11.11%) patient with EZH2 mutation, and 2 (22.22%) patients with unknown status.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      The mechanisms of primary resistance to EGFR-T790M may be highly heterogeneous. BCL2L11 loss, MET amplification, ERBB2 amplification, PTEN mutations, EZH2 mutations might contribute to molecular mechanisms of primary resistance to osimertinib in EGFR-T790M NSCLC. Further investigations are warranted to overcome these primary resistances.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      The authors.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

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