Frontiers in Oncology (Nov 2022)

Case report: BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib in ALK-rearranged lung adenocarcinoma

  • Thomas Pasau,
  • Els Wauters,
  • Els Wauters,
  • Isabelle Wauters,
  • Isabelle Wauters,
  • Fabrice Duplaquet,
  • Lionel Pirard,
  • Claudia Pop-Stanciu,
  • Nicky D’Haene,
  • Michael Dupont,
  • Thierry Vander Borght,
  • Benoît Rondelet,
  • Sebahat Ocak,
  • Sebahat Ocak

DOI
https://doi.org/10.3389/fonc.2022.985446
Journal volume & issue
Vol. 12

Abstract

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Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA ALK-rearranged lung adenocarcinoma who developed a BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of BRAF A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of BRAF mutation in NSCLC, and BRAF A598-T599insV mutation in other cancers.

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