Anaplastic thyroid carcinoma (ATC) accounts for approximately half of thyroid cancer-related deaths. It presents as a rapidly growing tumor which often invades locoregional structures and spreads to distant sites. And its disease entity is highly aggressive with an extremely poor prognosis. Although total thyroidectomy is one option of the initial treatment, some patients present with unresectable disease. And no effective systemic therapies with conventional chemotherapy regimens exist for ATC. From the previous molecular analysis BRAF mutations are frequently observed in 60%–80% of papillary thyroid carcinoma (PTC) and 30%–45% of ATC. BRAF and MEK inhibitors (Dabrafenib and Trametinib) were approved by Japan FDA in November 2023 for solid tumors with BRAF mutations which were refractory to standard treatment. We administered a combination therapy consisting of Dabrafenib and Trametinib to advanced ATC with BRAF mutation.

In this case series, we report four cases of unresectable anaplastic thyroid carcinoma with BRAF V600E mutation that were treated with a combination of Dabrafenib and Trametinib. The patients were initially treated with other treatments and were switched to Dabrafenib and Trametinib after testing positive for BRAF mutation. The tumor shrinkage was observed and even a conversion surgery could be completed in one case. These cases emphasize the importance of BRAF gene testing at initial diagnosis and the potential of BRAF and MEK inhibitors as treatment options for unresectable anaplastic thyroid carcinoma with BRAF mutations. The manageable adverse events profile of these medications makes them suitable for outpatient treatment. In conclusion, BRAF gene testing should be performed at initial diagnosis, and the treatment with BRAF and MEK inhibitors should be considered in mutation positive cases of anaplastic thyroid carcinoma.