On January 14, 2019, the U.S. Food and Drug Administration (FDA) approved cabozantinib (Cabometyx) for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
Approval was based on CELESTIAL (NCT01908426), a randomized (2:1), double-blind, placebo-controlled, multicenter trial in patients with HCC who had previously received sorafenib and had Child Pugh Class A liver impairment. Patients were randomized to receive cabozantinib 60 mg orally once daily (n=470) or placebo (n=237) until disease progression or unacceptable 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 eight 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.
The most common adverse reactions in ≥ 25% of patients who received cabozantinib in clinical trials, in order of decreasing frequency, are diarrhea, fatigue, decreased appetite, palmar-plantar erythrodysesthesia, nausea, hypertension, and vomiting.
The recommended cabozantinib dose is 60 mg orally, once daily at least one hour before or two hours after eating.
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.
In collaboration with the FDA and as a service to our members, ONS provides updates on recent FDA approvals and other important FDA actions (e.g., updated safety information, new prescribing information) pertaining to therapies for patients with cancer. This allows the agency to inform oncologists and professionals in oncology-related fields in a timely manner. Included in the FDA updates is a link to the product label or to other sites for additional relevant clinical information. In supplying this information, ONS does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described.