FDA approves Tafinlar-Mekinist combination for BRAF-mutated anaplastic thyroid cancer

The FDA extended approval of dabrafenib plus trametinib for the treatment of patients unresectable or metastatic anaplastic thyroid cancer with BRAF V600E mutations.

This combination of dabrafenib (Tafinlar, Novartis) and trametinib (Mekinist, Novartis) is indicated for patients with BRAF V600 mutation-positive metastatic melanoma, as well as BRAF V600E mutation-positive non-small cell lung cancer.

The FDA based this extended approval for thyroid cancer on a trial of patients with rare cancers with the BRAF V600E mutation, including 23 evaluable patients with anaplastic thyroid cancer.

Overall response rate served as the primary endpoint.

Of the evaluable patients with anaplastic thyroid cancer, 57% experienced a partial response and 4% experienced a complete response. Researchers did not observe significant tumor growth for 6 months or longer among nine of the 14 responding patients.

“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,” 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, said in a press release. “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.”

Researchers observed a safety profile that was consistent with previous studies of the combination. Common side effects included 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 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 drugs may cause harm to a developing fetus.

The FDA previously granted this combination orphan drug designation, priority review designation and breakthrough therapy designation for anaplastic thyroid cancer.