Author of

• 18974

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  P3.02 - Biology/Pathology (ID 620)

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

  • 23981

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    P3.02-033 - Pathological and Molecular Alterations after First and Second Generation EGFR-TKI Therapy in Patients with EGFR-Mutated Lung Adenocarcinomas (ID 8531)

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

    Background:
    Molecular alterations, including EGFR T790M point mutation and MET gene amplification, are reported as resistance mechanisms to first and second-generation EGFR tyrosine kinase inhibitors (TKIs). However, pathological transformation after EGFR-TKI administration has not been adequately studied. We compared the pathological alterations before and after EGFR-TKI administration in patients with EGFR-mutated lung adenocarcinomas.
    
    Method:
    Between January 2016 and March 2017, 61 patients received first and second generation TKI therapy for EGFR-mutation–positive lung adenocarcinomas or adenosquamous carcinomas. Among them, 31 patients experienced recurrence, and 22 of these patients, for whom diagnosis was confirmed through re-biopsy, were included in this study. Pathological and molecular alterations in the re-biopsy specimens were analyzed for these patients. Based on the 2015 WHO classification, lepidic predominant lung adenocarcinomas were categorized as low grade, papillary or acinar lung adenocarcinoma as intermediate grade, and micropapillary or solid lung adenocarcinoma as high grade.
    
    Result:
    The EGFR T790M mutation was positive in 11 of the 22 patients. Seven patients were cytologically diagnosed by pleural and cerebrospinal fluid analysis, as well as by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA). The remaining 15 patients underwent pathologically analysis. Twelve patients were found to have adenocarcinomas, two had large-cell neuroendocrine carcinomas (LCNECs), and one displayed epithelial-mesenchymal transition (EMT). Of the 12 adenocarcinomas analyzed, eight were the same tumor grade before and after TKI therapy, and four were higher grade than before TKI therapy.Figure 1
    
    
    
    Conclusion:
    Neuroendocrine and epithelial-mesenchymal transformations have an important role in EGFR-TKI resistance mechanisms, as previous reports have shown. Regarding the re-biopsy specimens, in one third of cases, the adenocarcinomas were of a higher tumor grade than the specimens analyzed before EGFR-TKI therapy.