Abstract
BACKGROUND: BRAF V600E mutation is a key oncogenic driver commonly found in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC). Dabrafenib plus trametinib combination therapy targeting this mutation has shown promising activity in clinical trials. This study aimed to verify the real-world effectiveness of this combination therapy in patients with BRAF V600E-positive PTC and ATC. METHODS: We retrospectively investigated adult patients with BRAF V600E-positive PTC and ATC who were treated with dabrafenib plus trametinib at a single university hospital in Japan. RESULTS: Between January 2024 and December 2024, 10 patients with PTC and 6 patients with ATC were identified, among whom 13 patients (81%) had been previously treated with lenvatinib. An objective response was observed in 5 patients with PTC (50%) and 4 patients with ATC (67%). The median progression-free survival and overall survival were not reached in patients with PTC, and were 2.7 months and 3.6 months, respectively, in patients with ATC. Partial regression of intracranial metastatic tumors was observed in 1 of the 2 patients with brain metastases at baseline. Rechallenge with another BRAF/MEK inhibitor combination therapy, encorafenib plus binimetinib, was attempted in 2 patients with ATC and demonstrated clinically meaningful responses. CONCLUSIONS: Dabrafenib plus trametinib combination therapy demonstrated clinical effectiveness in patients with BRAF V600E-positive thyroid cancer, with response rates comparable to those observed in clinical trials. However, tumor shrinkage did not appear to translate into improved survival in patients with ATC, highlighting the limitations of current targeted therapies in managing this aggressive subtype.