Author of

• 18975

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  P3.01 - Advanced NSCLC (ID 621)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23904

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    P3.01-045 - Correlation of EGFR Mutation Detection in CtDNA by Two Different Platforms in Advanced NSCLC Patients from a Single Institution (ID 9475)

    09:30 - 09:30  |  Author(s): R. Reyes
    • Abstract

    Background:
    Circulating-free tumor DNA (ctDNA) has emerged as a sensitive and feasible non-invasive blood-based approach alternative to tissue biopsies to screen for genetic drivers in advanced non-small cell lung cancer (NSCLC) patients. Recently, the COBAS Mutation Test has been FDA-approved for the detection of EGFR mutation (EGFRm) in peripheral blood but other approaches are currently used in clinical practice. Here, we aimed to correlate two different platforms for EGFRm monitoring ctDNA in an enriched cohort of tissue-genetically phenotyped EGFRm advanced NSCLC patients.
    
    Method:
    Blood samples were prospectively obtained from an enriched cohort of EGFR+ advanced NSCLC patients. Formalin-fixed paraffin-embedded (FFPE) tumor was characterized by NGS (Ion AmpliSeq Lung Cancer Research Panel v.2) in all patients at diagnose. Plasma ctDNA derived from peripheral whole blood was evaluated by COBAS EGFR Mutation Test v2 and a Peptide Nucleic Acid (PNA) probe–based real-time polymerase chain reaction blinded to baseline tumor genotype. Diagnostic accuracy and concordance of both blood techniques was used for direct comparison with respect to the molecular status of FFPE tissue.
    
    Result:
    A total of 80 matched pairs of peripheral blood samples from 40 patients were collected. Baseline tissue NGS reported mutations at exon 19 del (n=23), exon 21 (n=10), exon 18 (n=2), exon 20 (n=2) and T790M (n=3). Four wild-type EGFR tumors were used as controls. Blood samples were obtained at diagnose (n=12) and during tyrosine-kinase inhibitor (TKi) treatment for monitoring (n=28). Overall, concordance between both blood-based techniques with respect tissue-NGS was 100% (4/4) for negative controls and 55% (20/36) for positive tissue-NGS samples. Detection based on PNA and COBAS was negative in 60% (24/40) and 32.5% (13/40) patients respectively. Among 19 samples negative by PNA at monitoring, COBAS allowed plasma EGFRm detection in 11 patients. At baseline, the only two negative samples patients by both techniques were found in patients with localized brain disease. Six patients had detectable driver T790M mutation; among three patients with T790M+ in tissue, COBAS allowed detection in plasma in one patient whereas none was identified with PNA. The other three patients had acquired T790M mutations identified only in blood, all by COBAS.
    
    Conclusion:
    In this prospective blinded validation cohort, both methods retained high specificity. However, major differences between techniques were observed for longitudinal monitoring of EGFRm in blood.