Papillary Thyroid Cancer Differentiating Into Anaplastic Carcinoma With Near-Complete Response to Targeted Dabrafenib/Trametinib Combination Therapy.

Anaplastic thyroid cancer is an extremely aggressive disease, which at diagnosis is presumed to be stage IV, has a one-year survival of <10%, and at present has no definitive therapy. The combination of dabrafenib/trametinib has recently been investigated in cancers with BRAF V600E mutations, such as anaplastic thyroid cancer, melanoma, non-small cell lung cancer, and cholangiocarcinoma, and has shown promise in treating these malignancies. We report a case of a 71-year-old male with anaplastic thyroid carcinoma with a significant tumor burden in the right upper lobe of the lung and severe sequela of his disease. He was found to have a BRAF V600E mutation and had a dramatic response to dabrafenib/trametinib therapy at full dose (dabrafenib 150 mg BID/trametinib 2 mg daily) that was sustained even with dose reductions (dabrafenib 100 mg BID/trametinib 1.5 daily). The dose had to be reduced due to the development of severe side effects (fevers and uveitis). Combination therapy had to be discontinued after two months. Compassionate use of pembrolizumab was then initiated as his tumor had a PDL1 expression level of 90%. After five cycles of pembrolizumab, he had a recurrence of his disease. This case demonstrates the possible benefit of dabrafenib/trametinib combination therapy for some patients with anaplastic thyroid carcinoma who harbor BRAF V600E mutation and highlights some characteristic side effects of targeted therapy with BRAF/MEK inhibition with pyrexia and uveitis.