FDA Approves Dual Drug Treatment for Anaplastic Thyroid Cancer (ATC)

Today, the US Food and Drug Administration (FDA) approved a pair of drugs -- dabrafenib (Tafinlar) and trametinib (Mekinist). The two have been developed to be administered together to treat anaplastic thyroid cancer (ATC) that has spread to other parts of the body (metastatic) or cannot be removed by surgery and has a type of abnormal gene, BRAF V600E (BRAF V600E mutation-positive).

While both dabrafenib and trametinib can be used alone, they can also be used in combination to treat BRAF V600 mutation-positive metastatic melanoma and BRAF V600E mutation-positive, metastatic non-small cell lung cancer.

An open-label clinical trial of patients with rare cancers with the BRAF V600E mutation demonstrated the efficacy of dabrafenib and trametinib in treating ATC. Trials in BRAF V600E mutation-positive, metastatic melanoma or lung cancer and results in other BRAF V600E mutation-positive rare cancers produced positive outcomes seen in ATC patients. The percent of patients with a complete or partial reduction in tumor size (overall response rate) was the main measure. Fifty-seven percent of 23 evaluable patients experienced a partial response, and 4% experienced a complete response. In nine (64%) of the 14 patients with responses, there were no significant tumor growths for 6 months or longer.

Side effects of dabrafenib and trametinib patients correlate with those seen in other cancers when 2 drugs are used in combination. Fever (pyrexia), rash, chills, headache, joint pain (arthralgia), cough, fatigue, nausea, vomiting, diarrhea, myalgia (muscle pain), dry skin, decreased appetite, edema, hemorrhage, high blood pressure (hypertension) and difficulty breathing (dyspnea) include such common side effects.

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 include severe side effects of dabrafenib.

Severe side 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.

Pregnant women should seek advice regarding potential risks to the fetus and effective contraception methods as dabrafenib and trametinib can cause harm to a developing fetus.

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, states his excitement for the drug’s approval in a press release. “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. 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.”

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