On May 4, 2018, the FDA approved the combination of TAFINLAR® (dabrafenib) and MEKINIST® (trametinib) for the treatment of patients with anaplastic thyroid cancer (ATC) whose tumors harbor a BRAF V600E mutation . ATC is a rare and deadly malignancy composed of highly undifferentiated thyroid cells . BRAF mutations have been identified in about 11% of ATC samples and additional mutations in genes involved in the mitogen-activated protein kinase (MAPK) pathway are found in about 20% of ATC samples . Constitutively active MAPK pathway signaling supports tumor cell proliferation and survival, thus, some patients with ATC may benefit from MAPK pathway blockade via tyrosine kinase inhibitors (TKIs) dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor). Combination therapy of dabrafenib and trametinib has already been approved by the FDA for the treatment of unresectable or metastatic BRAF V600E/K-positive melanoma, adjuvant treatment for completely resected stage III BRAF V600E/K melanoma, and metastatic BRAF V600E-positive non-small cell lung cancer .
The approval to treat patients with BRAF V600E-positive ACT was based on results from a nine-cohort, non-randomized, open-label trial investigating the anti-tumor efficacy of the combination in patients with rare cancers with the a BRAF V600E mutation, including locally advanced, unresectable, or metastatic ATC (NCT02034110) . The overall response rate in patients with ATC, was 61% (N=23) with 64% of responses lasting longer than 6 months . Adverse events reported in patients with ATC were similar to those reported in other indications. This approval of dabrafenib and trametinib therapy provides a durable therapeutic option to patients with limited therapeutic options available.
- MEKINIST® (trametinib) tablets, for oral use. Drugs@FDA: FDA Approved Drug Products
05/04/2018 [cited 2018 May 9]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204114Orig1s009lbl.pdf.
- Tiedje, V., et al., Anaplastic thyroid carcinoma: review of treatment protocols. Endocr Relat Cancer, 2018. 25(3): p. R153-r161.
- Tiedje, V., et al., NGS based identification of mutational hotspots for targeted therapy in anaplastic thyroid carcinoma. Oncotarget, 2017. 8(26): p. 42613-42620.
- Efficacy and Safety of the Combination Therapy of Dabrafenib and Trametinib in Subjects With BRAF V600E- Mutated Rare Cancers. ClinicalTrials.gov March 30, 2018 [cited 2018 May 9]; Available from: https://clinicaltrials.gov/ct2/show/NCT02034110.