Author of

• 18374

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  P3.02b - Poster Session with Presenters Present (ID 494)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18492

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    P3.02b-118 - Potential Mechanism Revealed by Targeted Sequencing from Lung Adenocarcinoma Patients with Primary Resistance to EGFR-TKIs (ID 6236)

    14:30 - 14:30  |  Author(s): Y. Zhang
    • Abstract

    Background:
    Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKIs) has greatly improved the prognosis of lung adenocarcinoma. However, there are still approximately 20% lung adenocarcinoma patients with EGFR sensitive mutations that were primary resistance to EGFR-TKIs treatment The underlying mechanism is unknown.
    
    Methods:
    This study explored the mechanisms of primary resistance by analyzing 11 paired patients with corrsponding primary resistance (PFS<3months or without objective response) and sensitivity（PFS>12months）to EGFR-TKIs by next-generation sequencing (NGS). NGS targeted sequencing was performed on the Illumina X platform for 483 cancer-related genes. EGFR mutation was detected by ARMS initially.
    
    Results:
    Potential primary resistance mechanism was revealed by high frequency mutations unique in EGFR-TKIs resistance group. Among the 11 patients, 54.55% (6/11) carried known resistance mechanism, (2 patients carried MET amplification; 2 patients carried T790M mutation; 1 patient carried Her2 amplification; 1 patient carried PTEN loss). And 45.45%（5/11） carried novel mutations that may lead to drug resistance (2 patients carried TGFBR1 mutation; 1 patient carried TMPRSS2 fusion gene; 1 patient both have BIM deletion polymorphism and EGFR uncommon mutation). By analyzing somatic single-nucleotide mutation patterns, we found the frequency of C:G→T:A transitions in primary resistance group was significantly higher than that in sensitive group（0.54 vs 0.39, P=0.012）.
    
    Conclusion:
    The mechanism of EGFR-TKIs primary resistance is sporadic. TGFBR1 mutation, TMPRSS2 fusion gene and EGFR multiple mutations might be associated with EGFR-TKIs primary resistance. Cytosine spontaneous deamination （C:G→T:A）was positively associated with EGFR-TKIs primary resistance.