The approval should have a profound impact on patients with the rare tumor, according to experts.
For the first time, oncologists will have an approved treatment regimen to offer patients with BRAF-positive anaplastic thyroid cancer. On May 4, 2018, the US Food and Drug Administration (FDA) approved dabrafenib (Tafinlar) and trametinib (Mekinist) administered together, for the treatment of metastatic ATC and nonresectible anaplastic thyroid cancer with BRAF V600E mutation.
“This is tremendous news for us. It is a rare tumor,” said Barbara Murphy, MD, a Professor of Medicine and Director of Head and Neck Oncology at Vanderbilt University in Nashville, Tenn. “It should have a tremendous impact.”
The combination therapy is the first FDA-approved treatment for patients with this aggressive form of thyroid cancer. However, it is the third cancer with this specific gene mutation that the drug combination has been approved to treat, according to Richard Pazdur, MD, the 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.
The dabrafenib-trametinib combination is approved for use, alone or in combination, to treat both BRAF V600 mutation-positive metastatic melanoma and 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, as well as results in other BRAF V600E mutation-positive rare cancers, provided confidence in the results seen in patients with anaplastic thyroid cancer, according to the FDA. The open-label trial measured the number of patients with a complete or partial reduction in tumor size. Of 23 evaluable patients, 57% experienced a partial response (PR) and 4% experienced a complete response (CR). Among the 14 patients with responses, 9 (64%) had no significant tumor growth 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 for which the two drugs are prescribed. Common side effects include pyrexia, rash, chills, headache, arthralgia, cough, fatigue, nausea, vomiting, diarrhea, myalgia, dry skin, decreased appetite, edema, hemorrhage, hypertension, and dyspnea.
“There are significant toxicities. The side effects are real, and you generally have around 20% [of patients] experience grade 3/4 toxicity. It means we have to work hard to keep these toxicities controlled,” Dr. Murphy said in an interview with Cancer Network.
Severe side effects of dabrafenib include the development of new cancers, growth of tumors in patients with BRAF wild-type tumors, serious bleeding problems, and other complications, according to the FDA. Severe side effects of trametinib include the development of new cancers, serious bleeding problems, inflammation of intestines, and other complications, according to the FDA.
The National Institute of Health estimates there will be 53,990 new cases of thyroid cancer and an estimated 2,060 deaths from the disease in the US in 2018. Anaplastic thyroid cancer accounts for about 1% to 2% of all thyroid cancers.