Treatment of Unresectable BRAF V600E, TERT-Mutated Differentiated Papillary Thyroid Cancer With Dabrafenib and Trametinib.

Complete surgical resection of differentiated papillary thyroid cancer (PTC) is associated with an excellent prognosis. However, for locally invasive PTC, disease-specific morbidity and mortality increases when microscopic margin negative resection (R0) or complete macroscopic resection (R1) is not feasible. Neoadjuvant dabrafenib and trametinib (DT) used in BRAF V600E-positive, unresectable anaplastic thyroid cancer has allowed for R0 or R1 resection and improved survival rates. We demonstrate feasibility of using neoadjuvant DT in a patient with BRAF V600E and TERT-mutated PTC for whom R0/R1 resection was initially aborted due to predicted unacceptable morbidity. The patient was treated with neoadjuvant DT for 5 months, at which time disease was undetectable on imaging with near resolution on final pathology; however, subsequent rapid recurrence after discontinuation of neoadjuvant DT occurred. Neoadjuvant DT offers promise in future cohorts of patients with locally invasive BRAF V600E and TERT-mutated PTC for whom neoadjuvant therapy can reduce surgical morbidity while still allowing for R0/R1 resection.