Anaplastic thyroid cancer (ATC) is a rare, aggressive malignancy with an annual incidence of 1 to 2 cases per million in the United States.1 ATC accounts for 1.6% of all thyroid cancers but has a much higher mortality rate compared with other thyroid cancer histologies, with a dismal median survival of 5 months and a 1-year survival rate of only 20%.2 The benefit of systemic therapy in advanced metastatic ATC has yet to be proven in a controlled randomized clinical trial. Several cytotoxic chemotherapy agents, including bleomycin, carboplatin, cisplatin, docetaxel, doxorubicin, and paclitaxel, used in various combinations, have been reported to have palliative benefit in small nonrandomized trials, but little impact on survival.1,3,4 As a result of the poor outcome and lack of effective therapy, there is an urgent need for the development of novel agents for the treatment of ATC.
The availability of increasingly low-cost rapid comprehensive genomic profiling (CGP) and the elucidation of critical pathways in tumorigenesis have identified potentially targetable molecular mutations in a number of cancers. As a result, a number of studied targeted agents have demonstrated antitumor activity in preclinical models of thyroid cancer.5–7 Despite these encouraging results, the benefits of these novel agents have not been demonstrated in clinical trials. Two phase II trials using the multikinase inhibitors sorafenib and pazopanib failed to show significant benefit.8,9 However, anecdotal reports of benefit with a number of these agents in ATC are found in literature.8–12 This report presents a patient with advanced refractory metastatic ATC who was found to have a BRAF V600E mutation through CGP, was subsequently treated with dabrafenib and trametinib, and experienced a response.
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