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

Clin Oncol (R Coll Radiol). 2023 Jan;35(1):e60-e66. doi: 10.1016/j.clon.2022.10.017. Epub 2022 Nov 12.

Abstract

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.

Keywords: BRAF mutation; anaplastic thyroid cancer; dabrafenib; trametinib.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Humans
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics
  • Retrospective Studies
  • Thyroid Carcinoma, Anaplastic* / drug therapy
  • Thyroid Carcinoma, Anaplastic* / genetics
  • Thyroid Carcinoma, Anaplastic* / pathology
  • Thyroid Neoplasms* / drug therapy
  • Thyroid Neoplasms* / genetics
  • United Kingdom

Substances

  • trametinib
  • dabrafenib
  • Proto-Oncogene Proteins B-raf