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

Pasau, Thomas;Wauters, Els;Wauters, Isabelle;Duplaquet, Fabrice;Ocak, Sebahat;et.al.
(2022) Frontiers in Oncology — Vol. 12, p. 985446 [1-6] (2022)

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Abstract
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 -rearranged lung adenocarcinoma who developed a 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 A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of mutation in NSCLC, and A598-T599insV mutation in other cancers.
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Pasau, T., Wauters, E., Wauters, I., Duplaquet, F., Pirard, L., Stanciu Pop, C. M., D’Haene, N., Dupont, M., Vander Borght, T., Rondelet, B., & Ocak, S. (2022). Case report: BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib in ALK-rearranged lung adenocarcinoma. Frontiers in Oncology, 12, 985446 [1-6]. https://doi.org/10.3389/fonc.2022.985446 (Original work published 2022)