Today, the U.S. Food and Drug Administration approved dabrafenib (Tafinlar) and trametinib (Mekinist), administered together, for the treatment of unresectable, metastatic, BRAF V600E mutation–positive anaplastic thyroid cancer. Anaplastic thyroid cancer accounts for about 1% to 2% of all thyroid cancers.
“This is the first FDA-approved treatment for patients with this aggressive form of thyroid cancer, and the third cancer with this specific gene mutation that this drug combination has been approved to treat,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This approval demonstrates that targeting the same molecular pathway in diverse diseases is an effective way to expedite the development of treatments that may help more patients.”
Both dabrafenib and trametinib are also approved for use, alone or in combination, to treat BRAF V600 mutation–positive metastatic melanoma. Additionally, dabrafenib and trametinib are approved for use, in combination, to treat BRAF V600E mutation–positive, metastatic non–small cell lung cancer.
The efficacy of dabrafenib and trametinib in treating anaplastic thyroid cancer was shown in an open-label clinical trial of patients with rare cancers with the BRAF V600E mutation. Data from trials in BRAF V600E mutation–positive, metastatic melanoma or lung cancer and results in other BRAF V600E mutation–positive rare cancers provided confidence in the results seen in patients with anaplastic thyroid cancer. The primary endpoint of the trial was overall response rate. Of 23 evaluable patients, 57% experienced a partial response and 4% experienced a complete response; in 9 (64%) of the 14 patients with responses, no significant tumor growth was seen for 6 months or longer.
The side effects of dabrafenib and trametinib in patients with anaplastic thyroid cancer are consistent with those seen in other cancers when the two drugs are used together. Common side effects include pyrexia, rash, chills, headache, arthralgia, cough, fatigue, nausea, vomiting, diarrhea, myalgia, dry skin, decreased appetite, edema, hemorrhage, hypertension, and dyspnea.
Severe side effects of dabrafenib include the development of new cancers; growth of tumors in patients with BRAF wild-type tumors; serious bleeding problems; heart problems; severe eye problems; fever that may be severe; serious skin reactions; high blood sugar or worsening diabetes; and serious anemia.
Severe side effects of trametinib include the development of new cancers; serious bleeding problems; inflammation of intestines and perforation of the intestines; blood clots in the arms, legs or lungs; heart problems; severe eye problems; lung or breathing problems; fever that may be severe; serious skin reactions; and high blood sugar or worsening diabetes.
Both dabrafenib and trametinib can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception.
The FDA granted Priority Review and Breakthrough Therapy designation for this indication. Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases, was also granted for this indication.
The FDA granted this approval to Novartis Pharmaceuticals Corporation.