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Sorafenib’s Survival Benefit in Advanced Hepatocellular Carcinoma

HCC patients who received sorafenib had significantly longer median survival and time to disease progression compared with those who received placebo.

Effective systemic therapy does not yet exist for patients with advanced hepatocellular carcinoma (HCC), but a new study highlights the potential role of sorafenib, an oral multikinase inhibitor of both vascular endothelial growth factor receptor and platelet-derived growth factor receptor.

The phase III, randomized, double-blind, placebo-controlled trial involved 602 patients from 121 centers in Europe, North America, South America, and Asia. All patients had advanced HCC (i.e., they had disease progression after surgical or locoregional therapies, or they were not eligible for such therapies). The dose of sorafenib tested was 400 mg twice daily. Primary outcomes were overall survival (defined as time from randomization until death from any cause) and time to symptomatic progression (defined as time from randomization to first documented symptomatic event). Secondary outcomes included time to radiologic progression, disease-control rate, and safety. All analyses were performed on an intent-to-treat basis.

A total of 321 deaths had occurred by the second preplanned interim analysis, at which time the study was stopped. Compared with the placebo group, the sorafenib group had a longer median survival (10.7 vs. 7.9 months; P<0.001), a longer time to radiographic progression (5.5 vs. 2.8 months; P<0.001), and a higher rate of disease control (43% vs. 32%; P=0.002). Median time to symptomatic progression was similar between the groups, as was the incidence of adverse events.

Comment: This large, well-designed, well-powered study demonstrated a modest survival benefit (about 3 months) among advanced HCC patients who received the systemic therapeutic agent sorafenib. Furthermore, the drug was well tolerated. Sorafenib was approved by the FDA for this indication in November 2007, and clinicians should consider the agent for HCC patients that meet treatment criteria. Future studies are needed to determine sorefenib’s benefit in earlier-stage HCC, in patients with more-advanced liver disease, in combination with surgical and locoregional therapies, and after liver transplantation to prevent HCC recurrence.

— Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology July 23, 2008

Citation(s):

Llovet JM et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008 Jul 24; 359:378.

• Original article (Subscription may be required)
• Medline abstract (Free)

Roberts LR. Sorafenib in liver cancer — Just the beginning. N Engl J Med 2008 Jul 24; 359:420.

• Original article (Subscription may be required)
• Medline abstract (Free)