ASCO: Sorafenib (Nexavar) Improves Survival in Primary Liver Cancer

For advanced hepatocellular carcinoma (HCC), a multitargeted kinase inhibitor has demonstrated a significant survival advantage. In a multinational, phase III, trial, patients treated with oral sorafenib (Nexavar) had a 44% improvement in median overall survival and a doubling of time to progression compared to patients randomized to placebo.
Sorafenib is the first agent ever to demonstrate a significant survival advantage in HCC, said the study's principal investigator, Josep M. Llovet, M.D., of Mount Sinai in New York, at the American Society of Clinical Oncology meeting.
"Sorafenib was well tolerated with manageable side effects," Dr. Llovet said. "Sorafenib is the new reference standard for systemic therapy of hepatocellular carcinoma patients."
Sorafenib targets enzymes involved in proliferation and angiogenesis. The agent was approved in the U.S. 18 months ago for treatment of advanced renal cell carcinoma.
Dr. Llovet presented results from the Sorafenib HCC Assessment Randomized Protocol (SHARP), a multinational, phase III, randomized and placebo-controlled trial. The trial involved 602 patients with advanced HCC and no prior exposure to systemic therapy. The patients were randomized to sorafenib at 400 mg BID or placebo. The primary endpoints were overall survival and time to progression.
The trial ended prematurely when a planned interim analysis revealed a statistically significant difference in the primary endpoint. Patients treated with sorafenib had a median overall survival of 46.3 weeks compared with 34.4 weeks for the placebo group. The difference translated into a hazard ratio of 0.69 favoring sorafenib (P=0.00058). Median time to progression was 24 weeks with sorafenib and 12.3 weeks with placebo (HR 0.58, P=0.000007).
The overall occurrence rate of serious adverse effects was similar between the sorafenib and placebo groups (52% vs 54%). The most common Grade 3-4 events were diarrhea (11% versus 2%), hand-foot skin reaction (8% versus 1%), fatigue (10% versus 15%), and bleeding (6% versus 9%).
The results have the potential to change clinical practice, commented William Blackstock, M.D., of Wake Forest University in Winston-Salem, N.C., who was moderator at Dr. Llovet's presentation.
"Despite being the third leading cause of cancer death worldwide, hepatocellular carcinoma has no standard care. That, however, may change," said Dr. Blackstock.