Subbiah V, et al. - Researchers here reported the efficacy and safety profile of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E–mutated anaplastic thyroid cancer. They recognized dabrafenib plus trametinib as the first regimen that demonstrated robust clinical activity in BRAF V600E–mutated anaplastic thyroid cancer. In addition, the combination therapy was well tolerated thereby representing a meaningful therapeutic advance for this orphan disease.

Methods

• This is a phase II, open-label trial; dabrafenib 150 mg twice daily and trametinib 2 mg once daily were administered to patients with predefined BRAF V600E–mutated malignancies until unacceptable toxicity, disease progression, or death.
• Investigator-assessed overall response rate was observed as the primary end point.
• Duration of response, progression-free survival, overall survival, and safety were assessed as secondary end points.

Results

• Researchers identified 16 patients with BRAF V600E–mutated anaplastic thyroid cancer who were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks).
• History of receiving prior radiation treatment and/or surgery was identified in all the patients; six had received prior systemic therapy.
• They observed the confirmed overall response rate of 69% (11 of 16; 95% CI, 41% to 89%), with 7 ongoing responses.
• As a result of a lack of events, median duration of response, progression-free survival, and overall survival were not reached, with 12-month estimates of 90%, 79%, and 80%, respectively.
• Hundred patients who were enrolled with seven rare tumor histologies comprised the safety population.
• Fatigue (38%), pyrexia (37%), and nausea (35%) were identified as the common adverse events.
• They identified no new safety signals.