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PMID (36419902)
Authors Pasau T, Wauters E, Wauters I, Duplaquet F, Pirard L, Pop-Stanciu C, D'Haene N, Dupont M, Vander Borght T, Rondelet B, Ocak S
Title Case report: BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib in ALK-rearranged lung adenocarcinoma.
Journal Vol Issue Date Pages Journal Short Title
Frontiers in oncology 12 2022 985446 Front Oncol
URL
Abstract Text 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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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK BRAF A598_T599insV lung adenocarcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK progressed after an initial response to Alecensa (alectinib) and was found to have acquired BRAF A598_T599insV (PMID: 36419902). 36419902