FDA Approves Targeted Therapy Combo for Thyroid Cancer

On May 4, the U.S. Food and Drug Administration (FDA) approved a combination of molecularly targeted therapeutics for the treatment of a certain type of thyroid cancer. Specifically, the FDA approved the use of dabrafenib (Tafinlar) in combination with trametinib (Mekinist) for treating patients who have anaplastic thyroid cancer that cannot be removed by surgery or that has metastasized, and that tests positive for a BRAF V600E gene mutation.

Low magnification micrograph of anaplastic thyroid carcinoma with a component of papillary thyroid carcinoma tall cell variant. Image by Nephron, via Wikipedia.

With 53,990 new cases of thyroid cancer expected to be diagnosed in the United States in 2018, the disease will account for just over 3 percent of the new cancer cases anticipated for the year, according to data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program.

Anaplastic thyroid cancer is a rare cancer that accounts for only 1 percent to 2 percent of all thyroid cancers in the United States. Before last week’s approval, the standard treatment options for patients diagnosed with the disease were surgery, radiotherapy, and cytotoxic chemotherapy. Even with treatment, however, patient outcomes were often poor because anaplastic thyroid cancer is highly aggressive; the one-year relative survival rate has been estimated to be between 20 percent and 40 percent.

Genomic analysis has shown that up to 50 percent of anaplastic thyroid cancers have activating BRAF V600 mutations, and the anticancer therapeutics in this new treatment combination target two different components of the BRAF signaling pathway. Dabrafenib targets BRAF proteins generated by BRAF V600 mutations, blocking the BRAF signaling pathway at its initiation. Trametinib blocks the activity of two proteins, MEK1 and MEK2, that function further downstream in the BRAF signaling pathway.

Dabrafenib and trametinib were tested in combination as a treatment for BRAF V600E mutation–positive anaplastic thyroid cancer because researchers had previously shown that combining the molecularly targeted therapeutics increased overall response rate, duration of response, progression-free survival, and overall survival among patients who had BRAF V600E mutation–positive melanoma compared with dabrafenib alone.

The approval of the dabrafenib/trametinib combination for BRAF V600E mutation–positive anaplastic thyroid cancer was based on results from a phase II clinical trial. According to the FDA statement, 57 percent of the 23 patients for whom there was evaluable data had partial tumor shrinkage and 4 percent had complete tumor shrinkage, giving an overall response rate of 61 percent.

Earlier results from the trial, which were published in the Journal of Clinical Oncology when the researchers had data from just 16 patients, led to 12-month estimates for progression-free survival and overall survival of 79 percent and 80 percent.

The dabrafenib/trametinib combination was previously approved by the FDA for treating BRAF V600 mutation–positive metastatic melanoma and for treating BRAF V600E mutation–positive metastatic non–small cell lung carcinoma. Therefore, BRAF V600E mutation–positive anaplastic thyroid cancer is the third type of cancer for which the dabrafenib/trametinib combination of molecularly targeted therapeutics has been approved.

Commenting on this, 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, “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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