The FDA has approved the use of cabozantinib (Cometriq, made by Exelixis) to treat metastatic medullary thyroid cancer. The drug is a kinase inhibitor that blocks the cancer-causing kinase proteins RET, MET, and VEGFR2—and is the first approved inhibitor of both MET and VEGFR signaling.
“Cometriq is the second drug approved to treat medullary thyroid cancer in the past two years and reflects FDA's commitment to the development and approval of drugs for treating rare diseases,” Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products, said in a news release. “Prior to [this] approval and the approval of Caprelsa in April 2011, patients with this rare and difficult-to-treat disease had limited therapeutic treatment options.”
In 2012, medullary thyroid cancer accounted for about four percent of all thyroid cancer cases in the U.S., and about 1,780 deaths, according to National Cancer Institute estimates.
The drug's application was reviewed in six months under the agency's priority review program, which provides for an expedited six-month review for drugs with the potential to offer major advances in treatment or that provide a treatment when no adequate therapy exists. Cometriq also received an Orphan Drug designation by the FDA because it is intended to treat a rare disease or condition.
The drug's safety and effectiveness were tested in a randomized Phase III clinical trial that included 330 patients with medullary thyroid cancer. Patients given Cometriq lived an average of 11.2 months without tumor growth, whereas those given a placebo lived an average of four months without tumor growth. Results also showed 27 percent of patients treated with Cometriq had reductions in tumor size lasting an average of 15 months, whereas patients who received the placebo saw no reductions. Treatment with Cometriq did not extend survival.
The label includes a Boxed Warning to note that severe and fatal bleeding and perforations and fistula in the colon occurred in some patients. The most common side effects were diarrhea; inflammation or sores of the mouth; hand-foot syndrome; weight loss; loss of appetite; nausea; fatigue; oral pain; graying or loss of hair color; bad taste; new or worsening high blood pressure; abdominal pain and constipation. The most common laboratory abnormalities included increases in liver enzymes, low calcium and phosphorus, decreased white blood cells and platelets.