Complete Response to Afatinib of an EGFR Exon 18 delE709_T710insD-Mutated Stage IV Lung Adenocarcinoma

  • Blandine Jelli Department of Pulmonology, Hôpital Erasme, Brussels, Belgium https://orcid.org/0000-0002-2601-4166
  • Olivier Taton Department of Pulmonology, Hôpital Erasme, Brussels, Belgium
  • Nicky D'Haene Department of Pathology, Hôpital Erasme, Brussels, Belgium
  • Myriam Remmelink Department of Pathology, Hôpital Erasme, Brussels, Belgium
  • Zita Mekinda Department of Pulmonology, Hôpital Erasme, Brussels, Belgium

Keywords

EGFR mutation, exon 18, delE709_T710insD, lung cancer, afatinib

Abstract

Introduction: Epidermal growth factor receptor (EGFR) mutations are frequently found in patients with lung adenocarcinomas, 90% being deletions in exon 19 or point mutation in exon 21. Three generations of tyrosine kinase inhibitors (TKIs) targeting EGFR mutations are available and have changed patient prognosis but less data is available on exon 18 mutations and their sensitivity to TKI therapy. Exon 18 delE709_T710insD accounts for 0.06% (16/27,294) of all EGFR mutations and is an oncogenic driver. Several partial responses to afatinib have been described.

Case description: We report the first case, to the best of our knowledge, of the complete response to afatinib of a 57-year-old patient with stage IV lung adenocarcinoma with a delE709_T710insD mutation in the EGFR gene detected by next-generation sequencing. Oral afatinib was prescribed and despite treatment interruptions and dosage tapering due to cutaneous adverse events, a complete response was achieved 12 months after treatment initiation and is currently maintained at 17 months.

Conclusion: When EGFR mutation is suspected, complete DNA sequencing of exons 18 to 21 should be carried out and we suggest that afatinib should be the first-line treatment for exon 18 delE709_T710insD-mutated advanced lung adenocarcinomas.

VIEW THE ENTIRE ARTICLE

References

  • Shi Y, Au JS, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol 2014;9:154–162.
  • Harrison P, Vyse S, Huang P. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer. Semin Cancer Biol 2020;61:167–179.
  • Kobayashi Y, Togashi Y, Yatabe Y, Mizuuchi H, Jangchul P, Kondo C, et al. EGFR exon 18 mutations in lung cancer: molecular predictors of augmented sensitivity to afatinib or neratinib as compared with first- or third-generation TKIs. Clin Cancer Res 2015;21:5305–5313.
  • Ibrahim U, Saqib A, Atallah JP. EGFR exon 18 delE709_T710insD mutated stage IV lung adenocarcinoma with response to afatinib. Lung Cancer 2017;108:45–47.
  • Hirano T, Yasuda H, Tani T, Hamamoto J, Oashi A, Ishioka K, et al. In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non-small-cell lung cancer. Oncotarget 2015;6:38789–38803.
  • Wu JY, Shih JY. Effectiveness of tyrosine kinase inhibitors on uncommon E709X epidermal growth factor receptor mutations in non-small-cell lung cancer. Onco Targets Ther 2016;11:6137–6145.
  • Ackerman A, Goldstein MA, Kobayashi S, Costa DB. EGFR delE709_T710insD: a rare but potentially EGFR inhibitor responsive mutation in non-small-cell lung cancer. J Thorac Oncol 2012;7:e19–e20.
  • Iwamoto Y, Ichihara E, Hara N, Nakasuka T, Ando C, Umeno T, et al. Efficacy of afatinib treatment for lung adenocarcinoma harboring exon 18 delE709_T710insD mutation. Jpn J Clin Oncol 2019;49:786–788.
  • An N, Wang H, Zhu H, Yan W, Jing W, Kong L, et al. Great efficacy of afatinib on a patient with lung adenocarcinoma harboring uncommon EGFR delE709_T710insD mutations: a case report. Onco Targets Ther 2019;12:7399–7404.
  • D’Haene N, Le Mercier M, Salmon I, Mekinda Z, Remmelink M, Berghmans T. SMAD4 mutation in small cell transformation of epidermal growth factor receptor mutated lung adenocarcinoma. Oncologist 2019;24:9–13.
  • Published: 2021-08-11

    Issue: 2021: Vol 8 No 8 (view)

    Section: Articles

    How to cite:
    1.
    Jelli B, Taton O, D’Haene N, Remmelink M, Mekinda Z. Complete Response to Afatinib of an EGFR Exon 18 delE709_T710insD-Mutated Stage IV Lung Adenocarcinoma. EJCRIM 2021;8 doi:10.12890/2021_002749.