ASCO In a randomized phase III trial, patients with advanced, previously untreated hepatocellular carcinoma (HCC) treated with sorafenib (Nexavar) lived 44% longer than those treated with placebo and had a 73% prolongation in time to progression.
The findings represent a significant advance in the management of liver cancer, the fifth most common cancer globally and the third leading cause of cancer death. Lead investigator Joseph Llovet, MD, associate professor of medicine, and director, HCC Research Program, Mount Sinai School of Medicine, New York, reported the results in a plenary session at the 43rd Annual Meeting of the American Society of Clinical Oncology (abstract LBA-1).
The highly statistically and clinically significant overall survival outcome of the SHARP (Sorafenib HCC Assessment Randomized Protocol) study satisfied predetermined early stopping criteria for efficacy, Dr. Llovet reported.
Sorafenib, a multi-targeted tyrosine kinase inhibitor (TKI), was FDA approved in January 2006 for the treatment of advanced renal cell carcinoma. It is the only approved inhibitor of Raf kinase, which is overexpressed and activated in HCC. It also targets receptors for VEGF (vascular endothelial growth factor) and PDGF (platelet-derived growth factor), preventing tumor cell proliferation and neoangiogenesis.
The double-blind, placebo-controlled study was conducted from March 2005 to April 2006 at sites in the Americas, Europe, and Australia/New Zealand. Patients had advanced HCC and no prior systemic treatment, with at least one measurable untreated lesion, an ECOG performance status of 0-2, and Child-Pugh class A liver function status. A total of 299 patients received sorafenib at 400 mg twice daily, given until progression or adverse events requiring discontinuation, and 303 received placebo.
Baseline characteristics were similar for both groups, including median age (65 vs 66 years); sex (87% male in both arms); Child Pugh class A (95% vs 98%; the remainder were class B); and region (88% vs 87% European).