Sorafenib in advanced hepatocellular carcinoma.

Abstract (PubMed)

No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of VEGFR, PDGFR, and Raf, may be effective in hepatocellular carcinoma. We conducted a randomized, double-blind, placebo-controlled phase 3 trial (SHARP) in patients with advanced hepatocellular carcinoma who had not received prior systemic therapy. A total of 602 patients were randomized to receive sorafenib (400 mg twice daily) or placebo. The primary end points were overall survival and time to symptomatic progression. Median overall survival was 10.7 months in the sorafenib group versus 7.9 months in the placebo group (hazard ratio 0.69; 95% CI 0.55–0.87; P<0.001). Median time to radiologic progression was 5.5 months versus 2.8 months (P<0.001). Sorafenib significantly improved overall survival in patients with advanced hepatocellular carcinoma, establishing it as the first approved systemic therapy for this indication.