Background: Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and three, MET, and AXL, that are implicated within the advancement of hepatocellular carcinoma and the introduction of potential to deal with sorafenib, the conventional initial strategy to advanced disease. This randomized, double-blind, phase 3 trial evaluated cabozantinib compared to placebo in formerly treated patients with advanced hepatocellular carcinoma.
Methods: As many as 707 patients were at random assigned inside a 2:1 ratio to get cabozantinib (60 mg once daily) or matching placebo. Qualified patients had received previous treatment with sorafenib, had disease progression after a minumum of one systemic strategy to hepatocellular carcinoma, and could have obtained as much as two previous systemic regimens for advanced hepatocellular carcinoma. The main finish point was overall survival. Secondary finish points were progression-free survival and also the objective response rate.
Results: In the second planned interim analysis, the trial demonstrated considerably longer overall survival with cabozantinib compared to placebo. Median overall survival was 10.2 several weeks with cabozantinib and eight. several weeks with placebo (hazard ratio for dying, .76 95% confidence interval [CI], .63 to .92 P=.005). Median progression-free survival was 5.2 several weeks with cabozantinib and 1.9 several weeks with placebo (hazard ratio for disease progression or dying, .44 95% CI, .36 to .52 P<0.001), and the objective response rates were 4% and less than 1%, respectively (P=0.009). Grade 3 or 4 adverse events occurred in 68% of patients in the cabozantinib group and in 36% in the placebo group. The most common high-grade events were palmar-plantar erythrodysesthesia (17% with cabozantinib vs. 0% with placebo), hypertension (16% vs. 2%), increased aspartate aminotransferase level (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%).
Conclusions: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. The rate of high-grade adverse events in the cabozantinib group was approximately twice that observed in the placebo group.