FDA Approves Cabozantinib (Cometriq) for Metastatic Medullary Thyroid Cancer

The US Food and Drug Administration (FDA) has approved the tyrosine kinase inhibitor cabozantinib (Cometriq) for the treatment of metastatic medullary thyroid cancer, a rare type of thyroid cancer that makes up about 4% of all cases. The FDA has given the drug an orphan-product designation due to the rarity of the disease.

Cabozantinib, an oral drug previously known as XL-184, inhibits mutations in MET, VEGFR2, and RET, and in early studies showed the ability to inhibit angiogenesis, reduce metastases, and kill tumor cells.

“Cometriq is the second drug approved to treat medullary thyroid cancer in the past 2 years and reflects FDA’s commitment to the development and approval of drugs for treating rare diseases,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a press release. “Prior to today’s approval and the approval of Caprelsa in April 2011, patients with this rare and difficult to treat disease had limited therapeutic treatment options.”

It is estimated that in 2012, thyroid cancer will be diagnosed in 56,460 Americans and 1,780 will die from the disease, according to the National Cancer Institute. Medullary thyroid cancer develops in cells in the thyroid gland that make calcitonin, a hormone that helps maintain normal levels of calcium in the blood. Medullary thyroid cancer may occur spontaneously or in families with certain genetic mutations that can cause cancers of the endocrine system.

The 330-patient clinical trial that led to the approval, the EXAM trial, randomized medullary thyroid cancer patients in a 2:1 ratio to cabozantinib 140 mg daily (n = 219) or to placebo (n = 111). The study found that cabozantinib increased progression-free survival compared to placebo, 11.2 months vs 4 months, respectively (HR = 0.28; 95% confidence interval, 0.19–0.40; P < .0001).

Reductions in tumor size were seen in 27% of patients treated with cabozantinib, with results lasting an average of nearly 15 months. The study, however, did not find an increase in overall survival for patients in the experimental arm.

The prescribing information for cabozantinib includes a boxed warning due to the risk of perforations and fistula in the colon.

The most common adverse events associated with cabozantinib were diarrhea, mucositis, hand-foot syndrome, alopecia, unpleasant taste, anorexia, nausea, fatigue, oral pain, new or worsening hypertension, abdominal pain, and constipation.