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

Abstract

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.