Combined target therapy (dabrafenib and trametinib) in the treatment of metastatic BRAF ^V600E -positive anaplastic thyroid cancer: clinical cases

Anaplastic thyroid cancer (ATC) is a rare form of thyroid malignancy with a high aggressiveness and an extremely poor prognosis. Currently, two main models of ATC origin are considered: anaplastic carcinoma arises either from a patient’s pre-existing highly differentiated thyroid tumor cells through dedifferentiation, or de novo. Between 20 and 50% of ATC have activating V600E mutations in the BRAF gene. The combination of the two targeted drugs dabrafenib and trametinib has shown promising results in a number of rare cancers with V600E mutations in the BRAF gene, including a cohort of patients with BRAF-positive ATC. We present two clinical cases, namely the treatment of two patients, aged 74 and 71, in whom, against the background of highly differentiated thyroid carcinoma, dedifferentiation to ATC occurred. Molecular genetic analysis revealed a BRAF ^V600E mutation in both patients. Both patients have been receiving targeted therapy for more than 12 months according to the regimen: Dabrafenib 300 mg daily + trametinib 2 mg daily. Treatment was tolerated satisfactorily, without significant adverse events, no data for relapse or progression of the disease were obtained according to follow-up examination. Quality of life was maintained at a high level.
Conclusions. In recent years, the prognosis of BRAF-positive ATC has been improved by new drug therapies, such as targeted therapy. The low prevalence in the ATC makes it difficult to conduct large randomized clinical trials, making the need for international multicenter initiatives particularly important.

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