Author of

• 25463

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  Optimizing targeted therapy in lung cancer (ID 56)

  • Event: ELCC 2018
  • Type: Poster Discussion session
  • Track:
  • Presentations: 1
  • Moderators:F. Cappuzzo, N. Peled
  • Coordinates: 4/12/2018, 16:45 - 17:45, Room W

  • 25469

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    52PD - EGFR clonality and tumor mutation burden (TMB) analysis based on circulating tumor DNA (ctDNA) sequencing in advanced non-small cell lung cancer (NSCLC) (ID 351)

    16:45 - 17:45  |  Author(s): Y. Zang
    • Abstract

    Background:
    TKI has significantly improved survival time of NSCLC pts with sensitive mutation. However, pts present different outcome while receiving TKI treatment. We conduct a prospective multicenter clinical trial to determine whether clonality of sensitive mutation is related to the efficacy of TKI. We also evaluate the consistency of TMB between tissue and blood in this cohort.
    
    Methods:
    Paired tumor and plasma samples at diagnosis were obtained from systemic treatment naïve pts with advanced NSCLC. DNA was sequenced by target-capture deep sequencing of 1021 previously annotated genes related to solid tumors. Clonal EGFR mutation was defined if EGFR mutation was in the cluster with the highest mean variated allele frequency with PyClone, and otherwise subclonal EGFR mutation. TMB of tissue (tTMB) and blood (bTMB) analysis interrogated single nucleotide variants, small insertion and deletion, with VAF ≥3% and ≥0.5%, respectively. TMB-high pts were identified with ≥9 mut/MB (upper quartile of data from geneplus).
    
    Results:
    During February to November 2017, 80 advanced NSCLC pts were enrolled from 9 centers. A total of 371 somatic variations were detected in tissues. Mutations occurred most frequently in TP53 (52%), EGFR (47%), ALK (13%), KRAS (11%). In matched plasma, 258 (70%) tumor-derived mutations were detected by pan-caner panel sequencing. A total of 41 EGFR mutations were detected in 37 pts, most of which occurred in tyrosine kinase domain (Ex19del, 42%; L858R, 37%). Most EGFR mutation were clonal in tissue and plasma, with a consistence of 85% in paired samples. In addition, bTMB was significantly correlated to tTMB (Pearson r = 0.75, p-value = 2.3e-12), with a consistence of 90%. Interestingly, high TMB was observed in a small fraction of patients (6%) with driver mutations, such as mutations in EGFR, ALK fusion, ERBB2 and PIK3CA.
    
    Conclusions:
    Deep sequencing with the pan-cancer panel can effectively detect mutations and evaluate TMB in both tissue and blood with high consistence. EGFR mutations can be clonal or subclonal in both tissue and blood. Prospective multicenter study is ongoing to determine the EGFR clonality as a predictive factor for the TKI efficacy in NSCLC (TRACELib-NSCLC).
    
    Clinical trial identification:
    NCT03059641
    
    Legal entity responsible for the study:
    Shanghai Chest Hospital
    
    Funding:
    Geneplus-Beijing Institute
    
    Disclosure:
    All authors have declared no conflicts of interest.