BACKGROUND: Clinical benefit from cytotoxic chemotherapy for metastatic 
papillary thyroid carcinoma (PTC) is disappointing, and effective therapeutic 
approaches for these patients are urgently needed. Because kinase-activating 
mutations in the BRAF proto-oncogene commonly occur in advanced PTC, and 
inhibition of BRAF(V600E) has shown promising clinical activity in melanoma, 
BRAF inhibitor therapy may be an effective strategy to treat metastatic PTC.
METHODS: The dose escalation portion of a first-in-human, phase I study of 
vemurafenib, a selective RAF inhibitor, included three patients with metastatic 
PTC harboring the BRAF(V600E) mutation. Vemurafenib was initially dosed at 
240-360 mg twice a day, later escalated to 720 mg twice a day. Response 
evaluation was performed every 8 weeks per Response Evaluation Criteria in Solid 
Tumors (RECIST).
RESULTS: Among the three patients, one had a confirmed partial response with 
reduction of pulmonary target lesions by 31%, and the duration of response was 
7.6 months before the disease progressed in the lungs and the bones. The time to 
progression was 11.7 months. The other two patients had stable disease, and the 
time to progression was 13.2 and 11.4 months, respectively.
CONCLUSIONS: Vemurafenib appears to have a promising clinical activity in 
patients with metastatic PTC, and our data suggest that the BRAF(V600E) mutant 
kinase is a relevant target for therapy in this patient population. Further 
investigation of inhibitors of mutated BRAF kinase in patients with PTC in a 
phase II study is warranted.