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J. Longshore



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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      148P - Method comparison for detection of epidermal growth factor receptor (EGFR) T790M mutation in matched biopsied tumour sections and plasma samples (ID 172)

      12:30 - 13:00  |  Presenting Author(s): J. Longshore

      • Abstract
      • Slides

      Background:
      The correct identification of EGFR mutations is crucial to ensure that patients are assigned the most appropriate targeted treatment. Few studies have assessed EGFR mutation test performance in detecting the T790M resistance mutation in patients with advanced non-small cell lung cancer (NSCLC), using both biopsied tumour and plasma samples.

      Methods:
      We assessed the performance of the cobas® EGFR Mutation Test (v1 US-IVD, tissue; v2 CE-IVD, plasma), and therascreen® EGFR RGQ PCR Kit (CE-IVD v1, tissue) and EGFR Plasma RGQ PCR Kit (CE-IVD, plasma), using next-generation sequencing (NGS; Illumina MiSeq™) as the reference method. DNA was extracted from formalin fixed paraffin embedded tumour and plasma samples. Matched biopsy tumour tissue and plasma samples were taken from patients with advanced NSCLC and confirmed EGFR-tyrosine kinase inhibitor sensitising mutation, following disease progression on the most recent line of therapy, during screening for the AURA Phase II extension study.

      Results:
      288 tissue samples and 135 matched plasma samples were tested with the cobas® and therascreen tests, and compared with an NGS reference method (Table). When analysing tumour tissue, the two tests were similarly concordant for the detection of T790M, exon 19 deletions, and L858R mutation when using NGS as the reference. In our analysis, however, a higher invalid rate was observed with the therascreen test. When analysing plasma ctDNA, we observed a higher positive percent agreement with the NGS reference using the cobas® plasma test, indicating higher sensitivity for detection of EGFR mutations in plasma ctDNA, with similar specificity.Table: (Abstract 148P)

      Tumour tissue samples*NGS tissue test (reference)
      T790MEx19delL858R
      cobas tissue test n = 285PPA (95% CI)91 (86, 95)98 (95, 100)93 (86, 98)
      NPA (95% CI)98 (91, 100)91 (84, 96)100 (97, 100)
      therascreen tissue test n = 245PPA (95% CI)93 (88, 96)96 (92, 99)91 (82, 96)
      NPA (95% CI)97 (89, 100)89 (81, 95)99 (96, 100)
      Plasma samples*NGS plasma test (reference)
      T790MEx19delL858R
      cobas plasma test n = 135PPA (95% CI)92 (84, 97)97 (91, 100)86 (70, 95)
      NPA (95% CI)92 (80, 98)88 (77, 95)98 (93, 100)
      therascreen plasma test n = 133PPA (95% CI)65 (54, 75)77 (66, 86)76 (58, 89)
      NPA (95% CI)98 (89, 100)97 (88, 100)100 (96, 100)
      *Invalid results were excluded for the calculation of PPA and NPA. CIs were calculated using Clopper-Pearson exact method for binomial proportions. CI, confidence interval; Ex19del, exon 19 deletions; NGS, next-generation sequencing; NPA, negative percentage agreement (using NGS as the reference); PPA, positive percentage agreement (using NGS as the reference).

      Conclusions:
      When a viable test result is obtained using tumour tissue, the cobas® and therascreen tests appear to perform similarly for detection of EGFR mutations. When analysing plasma ctDNA, the cobas® test shows greater sensitivity compared to the therascreen test.

      Clinical trial identification:
      ClinicalTrials.gov NCT01802632

      Legal entity responsible for the study:
      AstraZeneca

      Funding:
      AstraZeneca

      Disclosure:
      S. Patel: Former employee of Qiagen and current employee of, and shareholder in, AstraZeneca. B. Collins: Consultancy fees from AstraZeneca. M. Cantarini: Shareholder in, former full-time employee of, and current part-time contractor for, AstraZeneca. S. Jenkins: Employee of, and shareholder in, AstraZeneca. All other authors have declared no conflicts of interest.

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