Cabozantinib Receives FDA Approval for Liver Cancer Treatment

On 14 January 2019, the United States Food and Drug Administration (FDA) approved cabozantinib (Cabometyx) for hepatocellular cancer (liver cancer) previously treated with sorafenib (Nexavar).

Approval is based on CELESTIAL, a 2-to-1 randomized, double-blind, placebo -controlled, multicenter clinical trial. Among previously sorafenib-treated liver cancer patients, 470 received once daily—1 dose—60 mg oral cabozantinib, while 237 received placebo, continuing until progression or unacceptable toxicity (adverse effects).

The infographic below shows approved advanced liver cancer treatments and comparisons:

According to CELESTIAL Results;

• Median overall survival was 10.2 months with cabozantinib and 8 months with placebo,
• Median progression-free survival (time treatment controlled disease) was 5.2 months with cabozantinib and 1.9 months with placebo,
• Cabozantinib reduced mortality risk by %24 compared with placebo,
• Objective response rates were %4 versus %0,4,
• Serious (grade 3. and 4.) adverse effects occurred in %68 with cabozantinib and %36 with placebo.
• The most common cabozantinib effects were palmar-plantar erythrodysesthesia (rash on e and feet), hypertension, raised blood AST, fatigue, and diarrhea. The recommended once-daily dose, taken at least 1 hour before or 2 hours after meals, is 60 mg cabozantinib.

Note: Cabometyx, containing cabozantinib, received FDA approvals in 2016 and 2017 for kidney cancer; Cometriq, also containing cabozantinib, was approved in 2012 for medullary thyroid cancer.

How Does Cabozantinib Work?

Cabozantinib inhibits cell growth and proliferation by suppressing tyrosine kinases VEGFR 1, 2, and 3, involved in new blood vessels feeding tumors, and MET and AXL. These pathways contribute to liver cancer progression and to resistance against sorafenib (Nexavar), standard first-line treatment for advanced liver cancer.