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Haley Kemp



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    FP07 - Pathology (ID 109)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP07.10 - Circulating Tumor DNA Analysis in NSCLC with MET exon 14 Skipping Alterations (ID 3418)

      00:00 - 00:00  |  Author(s): Haley Kemp

      • Abstract
      • Slides

      Introduction

      MET exon 14 skipping alteration (METex14) is an established oncogene driver in non-small cell lung cancers (NSCLC). Small molecule inhibitors (crizotinib, tepotinib, capmatinib and savolitinib) have shown efficacy in this patient population. Circulating tumor DNA (ctDNA) is an effective approach to detect METex14, as utilized in the VISION trial, which showed comparable outcome to tissue biopsy in patients treated with tepotinib. Here, we present the mutation and co-mutation landscape of the METex14 NSCLC detected by ctDNA.

      Methods

      Guardant360® results (Guardant Health) from patients with a diagnosis of advanced lung cancer were retrospectively reviewed and treatment-naïve and previously treated patients were included. Each subject was counted once regardless of multiple ctDNA tests performed. METex14 was considered positive when a deletion or non-synonymous mutation flanking exon 14 of MET was identified.

      Results

      A total of 345 lung cancer patients with METex14 were identified, including adenocarcinoma (79.1%), squamous cell carcinoma (9.8%), NSCLC NOS (7.8%), small-cell lung cancer (2%), and large-cell lung cancer (1.2%). The median age was 77 (range: 41-94) years, and 59% were female. The prevalence by functional sites were: 5’ splice donor site (45.8%), 3’ splice acceptor site (31.0%), D1010 splice mutation (18.3%), Y1003 – CBL mediated MET degradation (4.0%), others (0.9%). No significant gender differences were observed regarding the functional sites. The most frequent mutation type was base substitution (58.4%), followed by indel (41.6%). Whole-exon deletion was not found in this dataset (Table 1). The most frequent oncogene co-alterations included MET amplifications (9.0%), EGFR (7.2%) amplifications, KRAS mutation (6.9%, 15/24 subclonal), CDK4 (4.3%) amplifications and BRAF mutation (4.0%, 11/14 subclonal), while ALK-, ROS1-, RET-, and NTRK-fusions (1.4%) were uncommon. Additionally, TP53 mutations were detected in 53.8% of cases.

      Table 1. Functional site by mutation types of METex14 in lung cancer (N=345)
      n (%)
      Acceptor site 107 (31.0)
      Indel 96 (27.8)
      Base substitution 11 (3.2)
      Donor site 158 (45.8)
      Indel 46 (13.3)
      Base substitution 112 (32.5)
      Y1003 14 (4.0)
      Insertion 1 (0.3)
      Base substitution 13 (3.8)
      D1010 63 (18.3)
      Base substitution 63 (18.3)
      Others 3 (0.9)

      Conclusion

      In this real-world cohort of 345 cases of METex14-mutant NSCLC, detected using Guardant360, up to 21% were non-adenocarcinomas. The distribution of alterations of METex14 identified using liquid biopsy were similar to previously reported cohorts from tissue biopsies. Other driver oncogene alterations co-occur with METex14 at a low frequency.

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