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|Ref Type||Journal Article|
|Authors||Falchook GS, Millward M, Hong D, Naing A, Piha-Paul S, Waguespack SG, Cabanillas ME, Sherman SI, Ma B, Curtis M, Goodman V, Kurzrock R|
|Title||BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer.|
|Journal||Thyroid : official journal of the American Thyroid Association|
|Abstract Text||Mutations of v-raf murine sarcoma viral oncogene homolog B (BRAF) are commonly identified in papillary and anaplastic thyroid carcinoma and are associated with worse prognosis compared with the wild type. BRAF inhibition in papillary thyroid carcinoma cell lines and xenografts inhibits proliferation and decreases downstream phosphorylation. Our objectives were to analyze safety and efficacy of the selective BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid carcinoma.We present the subset of patients with BRAF-mutant thyroid carcinoma enrolled in a larger phase 1 study, the main results of which are reported elsewhere.Fourteen patients with BRAF(V600E)-mutant thyroid carcinoma were enrolled, of whom 13 (93%) had received prior radioactive iodine. The median duration on treatment was 8.4 months, and seven (50%) patients received treatment for ≥10 months. The most common treatment-related adverse events were skin papillomas (n=8, 57%), hyperkeratosis (n=5, 36%), and alopecia (n=4, 29%), all of which were grade 1. Treatment-related adverse events grade ≥3 included grade 4 elevated lipase and grade 3 elevated amylase, fatigue, febrile neutropenia, and cutaneous squamous cell carcinoma (n=1 for each). Four (29%) partial responses were observed, and nine (64%) patients achieved at least 10% decrease. Only one responder progressed while on the study drug after a response duration of 9.3 months. The other three responders had not progressed, with response duration of 4.6+, 10.4+, and 21.4+ months. With seven (50%) patients showing no progression at the time of study completion, the median progression-free survival was 11.3 months.Dabrafenib was well tolerated and resulted in durable responses in BRAF-mutant differentiated thyroid carcinoma patients.|
|Molecular Profile||Treatment Approach|
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|BRAF V600E||thyroid gland carcinoma||predicted - sensitive||Dabrafenib||Case Reports/Case Series||Actionable||In a Phase I trial, Tafinlar (dabrafenib) treatment resulted in a partial response in 29% (4/14) and stable disease in 43% (6/14) of patients with thyroid carcinoma harboring BRAF V600E, with 64% (9/14) of patients achieved at least a 10% decrease by RECIST, and a median progression-free survival of 11.3 months among responders (PMID: 25285888; NCT00880321).||25285888|