A phase II study reported by Subbiah et al in the Journal of Clinical Oncology indicates activity of the combination of dabrafenib (Tafinlar) plus trametinib (Mekinist) in patients with locally advanced or metastatic BRAF V600–mutant anaplastic thyroid cancer.
In the study, 100 patients with BRAF V600E–mutant rare cancers in 7of 9 prespecified histologies were enrolled at 47 sites worldwide between March 2014 and August 2016. Patients received dabrafenib at 150 mg twice daily and trametinib at 2 mg once daily until unacceptable toxicity or disease progression.
A total of 16 patients with BRAF V600E–mutant anaplastic thyroid cancer were evaluable for response. These patients had a median follow-up of 47 weeks; all had prior radiation therapy or surgery, and six had received prior systemic therapy. Confirmed overall response was observed in 11 patients (69%), with 7 responses ongoing at the time of analysis. The median durations of response, progression-free survival, and overall survival were not reached. Kaplan-Meier estimates at 12 months were 90% for ongoing response in responders, 79% for progression-free survival, and 80% for overall survival.
Safety data from the 100 patients enrolled with 7 rare tumor histologies showed that the most common adverse events of any grade were fatigue (38%), pyrexia (37%), and nausea (35%). Grade 3 or 4 adverse events occurred in 42% of patients, with the most common being fatigue, anemia, and neutropenia (all 5%).
The investigators concluded: “Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E–mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease.”
The study was funded by a grant from the National Institutes of Health and by Novartis Pharmaceuticals.
Bhumsuk Keam, MD, PhD, of Seoul National University Hospital, is the corresponding author of the Journal of Clinical Oncology article.
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