On January 14, 2019, cabozantinib (CABOMETYX, Exelixis, Inc.) was approved by the Food and Drug Administration for patients with hepatocellular carcinoma (HCC) who have previously been treated with sorafenib.
The approval was based on a randomized (2:1) CELESTIAL (NCT01908426), double-blind, placebo-controlled, multicenter study in HCC patients who had previously obtained sorafenib and had liver damage in Child Pugh Class A. Patients were randomized to receive either cabozantinib 60 mg once daily orally (n=470) or placebo (n=237) before worsening of disease or inappropriate toxicity.
The primary efficacy measure was overall survival (OS); additional outcome measures were progression-free survival (PFS) and overall response rate (ORR), as assessed by investigators per RECIST 1.1. Median OS was 10.2 months (95% CI: 9.1,12.0) for patients receiving cabozantinib and 8 months (95% CI: 6.8, 9.4) for those receiving placebo (HR 0.76; 95% CI: 0.63, 0.92; p=0.0049). Median PFS was 5.2 months (4.0, 5.5) and 1.9 months (1.9, 1.9), in the cabozantinib and placebo arms, respectively (HR 0.44; 95% CI: 0.36, 0.52; p<0.001). ORR was 4% (95% CI: 2.3, 6.0) in the cabozantinib arm and 0.4% (95% CI: 0.0, 2.3) in the placebo arm.
Diarrhea, fatigue, reduced appetite, palmar-plantar erythrodysesthesia, nausea, hypertension, and vomiting are the most common adverse reactions in about 25 percent of patients who received cabozantinib in clinical trials in order to minimize frequency.
The recommended dose of cabozantinib is 60 mg orally, at least 1 hour before or 2 hours after a meal, once a day.
FDA granted this application orphan drug designation. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.