Author of

• 30139

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  OA11 - Decomplexifying Molecular Targets, Immunotherapy and Treatment Settings in the Real World (ID 137)

  • Event: WCLC 2019
  • Type: Oral Session
  • Track: Treatment in the Real World - Support, Survivorship, Systems Research
  • Presentations: 1
  • Now Available
  • Moderators:Kumar Prabhash, Jyoti D Patel
  • Coordinates: 9/09/2019, 14:00 - 15:30, Interlaken (1988)

  • 30140

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    OA11.01 - Complex EGFR Mutations in Lung Adenocarcinoma (Now Available) (ID 2114)

    14:00 - 15:30  |  Presenting Author(s): Shang-Gin Wu
    • Abstract
    • Presentation
    • Slides

    Background
    

    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) provides a favorable treatment efficacy for EGFR-mutant lung cancer patients. Majority of EGFR mutations are a single mutation, including deletion in exon 19 (del-19) or L858R in exon 21. There is a subset of patients with complex EGFR mutations which contains two or more EGFR mutation types. It is unclear the treatment efficacy to different EGFR TKIs and survival prognosis for the complex EGFR-mutant patients due to small sample sizes of the prior studies. This study aimed to improve the understanding of the clinical characteristics and the prognosis of EGFR TKI treatment in lung adenocarcinoma patients with complex EGFR mutations.

    Method
    

    Between June 2005 to July 2018, patients harboring lung adenocarcinoma with complex EGFR mutations who were treated with EGFR TKIs were collected for EGFR mutation analysis by direct Sanger sequencing. Patients’ clinical characteristics, EGFR mutation status, treatment response, progression-free survival (PFS) and overall survival (OS) were analyzed. Patients harboring tumor with de novo T790M mutations were excluded for evaluation of EGFR TKI effectiveness.

    Result
    

    There were 175 patients (6.3%) with complex EGFR mutation from 2390 EGFR-mutant patients. Of the 175 complex EGFR-mutant patients, 122 patients who received EGFR TKIs were enrolled for evaluation of TKI effectiveness. Patients with the classical mutation pattern (del-19 or L858R) had higher treatment response rate (78.6% vs. 47.4%; p = 0.001) and PFS (8.6 months vs. 3.3 months; p = 0.006) than those without the classical mutations patterns (Fig-A). In multivariate analysis, female (p = 0.002), patients with disease relapse status, and the classical mutation patterns (p < 0.001) were associated with prolonged PFS. Compared with gefitinib and erlotinib, afatinib had a longer PFS, especially for patients without the classical mutation patterns. For OS, multivariate analysis revealed that female (p < 0.001), patients harbored classical mutation pattern (p = 0.001) (Fig-B), and patients with disease relapse status had longer OS. There were 51 patients who had re-biopsy tissue samples after acquired resistance to EGFR TKIs, 17 (33.3%) samples harbored T790M. In addition, small cell lung cancer transformation was detected in 3 (2%) patient’s re-biopsy tissue samples.

    

    Conclusion
    

    Female patients with complex EGFR-mutant lung adenocarcinoma and the classical mutation patterns have higher response rate, longer PFS and OS than those without the classical mutation patterns. Afatinib was active in lung adenocarcinoma harboring complex EGFR mutations, and may especially benefit patients without the classical mutation patterns due to longer PFS results.

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