Cabozantinib (Cometriq; Exelixis) is the second drug ever to be approved by the FDA for the treatment of patients with metastatic medullary thyroid cancer. Cabozantinib is a kinase inhibitor that blocks the abnormal kinase proteins that are involved in the development and growth of medullary cancer cells. Patients should not eat for at least 2 hours before and 1 hour after taking cabozantinib. Cabozantinib received an orphan drug designation.
“Prior to today’s approval and the approval of Caprelsa [vandetanib] in April 2011, patients with this rare and difficult-to-treat disease had limited therapeutic treatment options,” said Richard Pazdur, MD.
The FDA completed its review of cabozantinib’s application in 6 months, using its priority review program, because of the scarcity of treatments for this rare disease. In 2012, the National Cancer Institute estimated that 56,460 Americans would be diagnosed with thyroid cancer and 1780 would die from the disease; approximately 4% of thyroid cancers are medullary, rendering it a rare type of thyroid cancer.
Medullary thyroid cancer develops in cells in the thyroid gland that make calcitonin, a hormone that helps to maintain optimal levels of calcium in the blood. This type of cancer may occur spontaneously or in families with certain genetic mutations that result in ≥1 cancers of the endocrine system, including the thyroid gland.
The safety and effectiveness of cabozantinib were established in a clinical study involving 330 patients with medullary thyroid cancer. The use of cabozantinib increased the length of PFS and, in some patients, improved the response rate.
PFS was an average of 11.2 months in patients who received cabozantinib compared with an average of 4.0 months in patients receiving a placebo. In addition, 27% of patients receiving cabozantinib have reductions in tumor size lasting an average of nearly 15 months; no reductions in tumor size were seen in patients who received a placebo. There was no improved OS with the active drug.
The most common side effects are diarrhea, inflammation or mouth sores, 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 include increases in liver enzymes, low calcium and phosphorus levels, and decreased white blood cells and platelets.
The FDA approved cabozantinib with a Boxed Warning regarding the risk for severe and fatal bleeding and perforations and fistula in the colon. (November 29, 2012)
