Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer
Journal of Investigative Medicine High Impact Case Reports
anaplastic thyroid cancer; BRAF inhibitor; BRAF V600E; CDK4 mutation; EZH2 mutation; mitogen-activated extracellular protein kinase inhibitor (MEK inhibitor); targeted therapy
© 2019 American Federation for Medical Research. Context. Anaplastic thyroid cancer (ATC) is an aggressive tumor with a median survival of 3 to 9 months, a 1-year survival of less than 10% and without definitive therapies. Recently, in BRAF V600E mutated ATCs, new targeted therapy using a combination of a BRAF inhibitor, dabrafenib (Dab), with a mitogen-activated extracellular protein kinase (MEK) inhibitor, trametinib (Tram), has shown significant promise. Case Description. We report a case of aggressive ATC with 5 sequence mutations: BRAF V600E (mutation fraction [MF] 34%), TERT E441del (MF 37%), RET N579K (MF 55%), EZH2 D154E (MF 60%), and CDK4 S259L (MF 48%). The patient had a dramatic response to the Dab/Tram combination with near complete resolution of his lung, bone, hepatic, and splenic lesions soon after starting therapy. Unfortunately, intolerable side effects (grade 2-3) on this regimen required tapering and discontinuation of the treatment. He had a quick resurgence of disease after stopping the combination therapy. The patient died approximately 3 months after discontinuing Dab/Tram. Autopsy revealed an atrophic thyroid gland with microscopic subcapsular focus of well-differentiated papillary thyroid carcinoma. There was extensive lymphatic spread of the tumor throughout bilateral lungs with fibrosis. No other metastatic site was identified. Conclusion. We report a unique case of ATC with 2 new mutations of EZH2 D154E and CDK S529L. This case exemplifies the significant promise Dab/Tram therapy holds, the potential side effects that limit their use, and autopsy findings status post use of this combination therapy.
Fazeli, S., Paal, E., Maxwell, J., Burman, K., Nylen, E., & Khosla, S. (2019). Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer. Journal of Investigative Medicine High Impact Case Reports, 7 (). http://dx.doi.org/10.1177/2324709619890942