FDA Approves Hepatocellular Carcinoma Therapy, Cabozantinib

The US Food and Drug Administration (FDA) has approved Exelixis’ cabozantinib (Cabometyx)for the treatment of patients with hepatocellular carcinoma (HCC) who previously received sorafenib (Nexavar).

Data from the phase 3 CELESTIAL trial evaluating cabozantinib patients with advanced HCC who previously received sorafenib served as the basis for the approval. Versus placebo, cabozantinib demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS). More specifically, patients treated with cabozantinib experienced a median OS of 10.2 months, while patients treated with placebo experienced a median OS of 8 months (HR .76, 95% CI .63-.92; p=.0049).

“Patients with this form of advanced liver cancer have few treatment options, particularly once their disease progresses following treatment with sorafenib,” Ghassan K. Abou-Alfa, MD, CELESTIAL lead investigator from Memorial Sloan Kettering Cancer Center, said in a statement.

At 5.2 months of treatment with cabozantinib, median progression-free survival (PFS) was more than doubled compared to placebo, which was 1.9 months (HR .44, 95% CI .36-.52; p<.0001). Per RECIST 1.1, objective response rates with cabozantinib were 4% compared to .4% with placebo (p=.0086). In addition, 64% of patients in the cabozantinib group achieved disease control (partial response or stable disease) compared with 33% of patients in the placebo group.

Observed adverse events in the CELESTIAL trial remained consistent with the known safety profile of cabozantinib. Compared to the placebo group, the most common (≥10%) grade 3 or 4 adverse events in the cabozantinib group consisted of palmar-plantar erythrodysesthesia (17% vs. 0%), hypertension (16%vs. 2%), increased aspartate aminotransferase (12% vs. 7%), fatigue (10% vs. 4%) and diarrhea (10% vs. 2%).

In 6 patients in the cabozantinib group, treatment-related grade 5 adverse events occurred (hepatic failure, esophagobronchial fistula, portal vein thrombosis, upper gastrointestinal hemorrhage, pulmonary embolism and hepatorenal syndrome). In the placebo group, 1 patient experienced hepatic failure. Discontinued treatment due to treatment-related adverse events occurred in 16% of patients in the cabozantinib arm and 3% of patients in the placebo.

“While we’ve seen some progress in the treatment of primary liver cancer in recent years, the patient community still needs new and better options,” said Andrea Wilson, president and founder of Blue Faery: The Adrienne Wilson Liver Cancer Association, in a recent statement. “The approval of CABOMETYX has been eagerly anticipated, making this an important day for patients diagnosed with this devastating disease.”