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

par Pasau, Thomas;Wauters, Els;Wauters, Isabelle ;Duplaquet, Fabrice;Pirard, Lionel;Stanciu-Pop, Claudia;D'Haene, Nicky ;Dupont, Michael;Vander Borght, Thierry;Rondelet, Benoît ;Ocak, Sebahat
Référence Frontiers in oncology, 12, 985446
Publication Publié, 2022-11

Article révisé par les pairs

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Résumé :

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.