Cabozantinib (CABOMETYX)

On April 25, 2016, the U. S. Food and Drug Administration approved cabozantinib (CABOMETYX, Exelixis, Inc.) for the treatment of advanced renal cell carcinoma in patients who have received prior anti-angiogenic therapy.

The approval was based on a randomized study in which patients with advanced renal cell carcinoma who had received prior anti-angiogenic therapy received either cabozantinib 60 mg orally once daily (N=330) or everolimus 10 mg orally once daily (N=328).

The primary endpoint was progression-free survival among the first 375 randomized subjects. Median progression-free survival in this group was 7.4 and 3.8 months in the cabozantinib and everolimus arms, respectively [HR 0.58 (95% CI: 0.45, 0.74); p<0.0001]. Median overall survival in the intent-to-treat population was 21.4 and 16.5 months in the cabozantinib and everolimus arms, respectively [HR 0.66 (95% CI: 0.53, 0.83); p=0.0003]. Confirmed response rate was 17% (95% CI: 13, 22) in the cabozantinib arm and 3% (95% CI: 2, 6) in the everolimus arm.

Safety was evaluated in 331 patients treated with cabozantinib. The most common (greater than or equal to 25%) adverse reactions included diarrhea, fatigue, nausea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, hypertension, vomiting, weight decreased, and constipation. Sixty percent of patients treated with cabozantinib had at least one dose reduction while on study. Serious adverse events were reported in 40% of patients. The most common serious adverse events (greater than or equal to 2%) were abdominal pain, pleural effusion, diarrhea, and nausea.

The recommended dose and schedule for cabozantinib is 60 mg orally daily.

This application was granted Breakthrough Therapy Designation, Fast Track, and Priority Review. It was approved prior to the Priority Review deadline of June 22, 2016. A description of these expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics available at:http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.

Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208692s000lbl.pdf