Sorafenib therapy in advanced hepatocellular carcinoma: the SHARP trial

Abstract

Until now, no effective systemic treatment options have been available for patients with unresectable advanced hepatocellular carcinoma (HCC). In the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP), patients with unresectable advanced HCC with Child–Pugh liver function class A and who had not received prior systemic therapy, received either oral sorafenib (400 mg twice daily) or placebo until radiological and symptomatic progression. The two groups of patients were well balanced with respect to baseline characteristics. The study was stopped at the second planned interim analysis because of an advantage in the median overall survival (10.7 vs 7.9 months; hazard ratio: 0.69; 95% CI: 0.55–0.87; p < 0.001) and the median time to radiological progression (5.5 vs 2.8 months; p < 0.001) in the sorafenib arm. However, sorafenib was not able to increase the time to symptomatic progression. In terms of toxicity, there were more cases of diarrhea, weight loss, hand–foot skin reaction and hypophosphatemia among the patients receiving sorafenib, the majority of which were of grade 1 or 2 severity. The SHARP trial has demonstrated that sorafenib is effective in prolonging median survival and time-to-progression in patients with advanced HCC and that it is generally well tolerated with a manageable adverse events profile.