Clinical

Sorafenib slows progression of advanced liver cancer

Last Updated: 2008-07-23 17:08:34 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Treatment of advanced hepatocellular carcinoma with the multiple kinase inhibitor sorafenib improved survival by about 3 months in a multinational, phase III clinical trial reported in the New England Journal of Medicine for July 24.

Sorafenib (Nexavar) is a bisaryl urea that inhibits tumor growth and neoangiogenesis by targeting growth factor receptors and Raf signaling. Early clinical trials indicated that single-agent sorafenib might have a therapeutic effect on hepatocellular carcinoma.

Dr. Josep M. Llovet at the Barcelona Clinical Liver Cancer Group in Spain and colleagues enrolled 602 patients with advanced hepatocellular carcinoma with well-preserved liver function (Child-Pugh class A). None had received previous systemic treatment.

Patients were randomly assigned to sorafenib 400 mg twice a day (n = 299) or placebo (n = 303). The trial was halted after 321 deaths had occurred (143 in the sorafenib group and 178 in the placebo group).

Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (p < 0.001). Median time to radiologic progression was 5.5 months and 2.8 months, respectively (p < 0.001). The survival benefit associated with sorafenib remained significant after adjustment for ECOG performance status, tumor burden and other prognostic factors (hazard ratio 0.73, p = 0.004).

Safety analysis indicated an increased incidence of diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia in the sorafenib group.

On the basis of these results, sorafenib was approved by European and US regulators in the final quarter of 2007 for treatment of advanced hepatocellular carcinoma.

"These results give hope for further advances in therapy during the exploration of the potential efficacy of sorafenib and other agents in combination with local or locoregional therapy," Dr. Lewis R. Roberts, from the Mayo Clinic in Rochester, Minnesota, writes in a related editorial.

However, with progress comes the attendant high cost of new targeted therapies: the monthly cost of sorafenib is US $5400, Dr. Roberts points out.

"This situation stresses the importance of worldwide public-private partnerships to... provide effective therapies to suffering patients at costs that are within their reach."

N Engl J Med 2008;359:378-390,420-422.