Dabrafenib and Trametinib Therapy for Advanced Anaplastic Thyroid Cancer – Real-World Outcomes From UK Centres

Aims Anaplastic thyroid cancer (ATC) is a rare but aggressive form of thyroid cancer with a median survival of 4 months. Recent advances in molecular profiling have shown that up to half of ATCs harbour the BRAF-V600E mutation. The aim of this study was to provide real-world data and experience on the use of combination therapy dabrafenib and trametinib in patients with BRAF-V600E-mutated advanced ATC. Materials and methods We retrospectively evaluated patients with confirmed BRAF-V600E-mutated ATC, defined as patients with locally advanced or metastatic ATC with no locoregional, radical treatment options. Outcomes measured were overall survival, progression-free survival, response rate, discontinuation rate, dose reduction rate and toxicity data. Results Seventeen patients were evaluated and the mean age was 68 years. Ten patients died by the time of censoring. The median duration of follow-up was 12 months (3–43 months). The estimated median overall survival was 6.9 months (95% confidence interval 2.46 months – upper confidence interval not reached) and the median progression-free survival was 4.7 months (95% confidence interval 1.4–7.8 months). Dose interruptions and/or reductions were common, but none of the patients had to permanently discontinue treatment because of toxicities. Severe toxicities (grades 3 and 4) were uncommon. Conclusions This study supports the indication of dabrafenib and trametinib in BRAF-V600E-mutated ATC as an effective and well-tolerated treatment in an historically difficult to treat cancer.