Response to Dabrafenib Plus Trametinib in a Patient With an Uncommon Activating BRAF Mutation: A First in Non–Small Cell Lung Cancer

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John A. Sharp Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH

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Daniel Jones Department of Pathology, The Ohio State University, Columbus, OH

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Julia K. Rotow Dana-Farber Cancer Institute, Boston, MA

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Panos M. Fidias Massachusetts General Cancer Center at Exeter Hospital, Exeter, NH

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Erin Bertino Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH
Columbus Oncology and Hematology Associates, Columbus, OH

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Dwight H. Owen Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH

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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.

Submitted October 3, 2023; final revision received December 19, 2023; accepted for publication January 16, 2024. Published online March 13, 2024.

Disclosures: Dr. Rotow has disclosed receiving institutional grant/research support from AstraZeneca, BioAtla, Blueprint Medicines, EpimAb Biotherapeutics, LOXO Oncology, Enliven, Redcloud, and ORIC Pharmaceuticals; serving as a principal investigator for AstraZeneca, BioAtla, Blueprint Medicines, EpimAb Biotherapeutics, LOXO Oncology, Enliven, Redcloud, and ORIC Pharmaceuticals; serving as a scientific advisor for Amgen, AstraZeneca, BioAtla, Bristol Myers Squibb, Daiichi Sankyo, Genentech, G1 Therapeutics, Guardant Health, Janssen, Jazz Pharmaceuticals, Sanofi/Genzyme, Summit Pharmaceuticals, and Takeda; serving as a consultant for Amgen, AstraZeneca, BioAtla, Daiichi Sankyo, Genentech, G1 Therapeutics, Guardant Health, Janssen, Jazz Pharmaceuticals, Sanofi/Genzyme, Summit Pharmaceuticals, and Takeda; and receiving honoraria from AstraZeneca. Dr. Bertino has disclosed serving on an advisory board for Novartis; and serving on a speaker’s bureau for Sanofi. Dr. Owen has disclosed receiving grant/research support from and serving as a principal investigator for Pfizer. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.

Supplementary material: Supplementary material associated with this article is available online at https://doi.org/10.6004/jnccn.2024.7009. The supplementary material has been supplied by the author(s) and appears in its originally submitted form. It has not been edited or vetted by JNCCN. All contents and opinions are solely those of the author. Any comments or questions related to the supplementary materials should be directed to the corresponding author.

Correspondence: John A. Sharp, MD, The Ohio State University Comprehensive Cancer Center, Division of Medical Oncology, Department of Internal Medicine, 1250A Lincoln Tower, 1800 Cannon Drive, Columbus, OH 43210. Email: john.sharp@osumc.edu

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