The FDA approved cabozantinib (Cabometyx) on Monday for the second-line treatment of hepatocellular carcinoma (HCC) in patients who progressed or were intolerant of sorafenib (Nexavar), drugmaker Exelixis announced.
CELESTIAL, the phase III study that led to the approval, randomized more than 700 patients to 60-mg cabozantinib daily or placebo, demonstrating improvements in both progression-free survival (PFS) and overall survival (OS) with the multikinase inhibitor.
Median PFS was 5.2 months in the cabozantinib arm compared with 1.9 months in the placebo arm (HR 0.44, 95% CI 0.36-0.52, P<0.0001), while median OS was 10.2 months versus 8.0 months, respectively (HR 0.76, 95% CI 0.63-0.92, P=0.0049).
Also improved with cabozantinib were rates of objective response by RECIST 1.1 criteria (4% vs 0.4%, P=0.0086) and disease control (64% vs 33%), which included patients who achieved either partial responses or stable disease.
“Patients with this form of advanced liver cancer have few treatment options, particularly once their disease progresses following treatment with sorafenib,” lead investigator Ghassan K. Abou-Alfa, MD, of Memorial Sloan Kettering Cancer Center in New York City, said in a statement from Exelixis. “Physicians are eager for new options for these patients, and the results of the CELESTIAL trial demonstrate that Cabometyx has the efficacy and safety profile to become an important new therapy.”
Cabozantinib, which was previously approved for treating renal cell carcinoma and metastatic medullary thyroid cancer (in a different formulation under the trade name Cometriq), joins nivolumab (Opdivo), regorafenib (Stivarga), and most recently pembrolizumab (Keytruda) as FDA-approved second-line therapies for HCC.
The most common grade 3/4 adverse events in CELESTIAL for cabozantinib and placebo, respectively, were hand-foot syndrome (17% vs 0%), hypertension (16% vs 2%), increased levels of aspartate aminotransferase (12% vs 7%), diarrhea (10% vs 2%), and fatigue (10% vs 4%).
More patients on the study drug discontinued treatment due to adverse events (16% vs 3%). In the cabozantinib arm, six patient deaths were deemed treatment-related compared with one in the placebo group.