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Ref Type Journal Article
PMID (38479107)
Authors Sharp JA, Jones D, Rotow JK, Fidias PM, Bertino E, Owen DH
Title Response to Dabrafenib Plus Trametinib in a Patient With an Uncommon Activating BRAF Mutation: A First in Non-Small Cell Lung Cancer.
Journal Vol Issue Date Pages Journal Short Title
Journal of the National Comprehensive Cancer Network : JNCCN 2024 Mar 13 1-5 J Natl Compr Canc Netw
URL
Abstract Text Mutations in BRAF are present in 4% of non-small cell lung cancer (NSCLC), of which half are well-characterized activating variants affecting codon 600 (classified as class I). These mutations, most commonly BRAF V600E, have been associated with response to BRAF/MEK-directed small molecule kinase inhibitors. NSCLC with kinase-activating BRAF mutations occurring at other codons (class II variants) represent a substantial portion of BRAF-mutated NSCLC, but use of targeted therapy in these tumors is still under investigation. Class II mutations have been described in other tumor types and have been associated with response to BRAF/MEK-targeted agents, although optimal treatment strategies for these patients are lacking. This report presents a case of a woman with metastatic NSCLC harboring a class II BRAF p.N486_P490del variant who had a sustained clinical response to combination therapy with dabrafenib and trametinib. This first report of the use of BRAF/MEK-targeted therapy for this variant in NSCLC supports consideration of such treatment for tumors with class II BRAF variants.

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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
BRAF N486_P490del lung adenocarcinoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in complete resolution of the pulmonary lesions and ongoing response after 6 months in a patient with metastatic lung adenocarcinoma harboring BRAF N486_P490del, who remained on treatment at 9 months (PMID: 38479107). 38479107