for Health Care Providers
Sorafenib: A Treatment for Advanced Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC), also known as primary liver cancer or hepatoma, is the 5th most common cancer in the world. HCC is much more common in Asia and other areas with high hepatitis B prevalence, but in the United States, the incidence has been rising steadily over the past two decades, in large part owing to the high prevalence of hepatitis C and aging of the hepatitis C patient population.
Effective treatments for HCC have been extremely limited. Early-stage HCC can be treated surgically with partial liver resection or liver transplant, which can result in lengthened survival. Until recently, no established treatment for advanced HCC has shown a survival benefit, yet HCC is detected most often at advanced stages of disease, so patients have had poor survival rates.
Recently, a systemic chemotherapy that increases survival time in advanced HCC has been found. Sorafenib, an oral medication that is administered twice daily, was originally used for treatment of renal cell carcinoma but has been shown to be the first treatment to extend survival time for nonsurgical HCC. The results of a Phase III trial (SHARP trial) were presented as an abstract at the American Society of Clinical Oncology Annual Meeting in June 2007 and the data were published in the New England Journal of Medicine in July 2008. SHARP was a large multicenter, randomized, placebo-controlled trial to study the efficacy and safety of sorafenib vs placebo in patients with HCC in advanced stages.
Results of the trial showed a statistically significant lengthened survival in sorafenib-treated patients compared with placebo-treated patients, all with unresectable HCC. The hazard ratio for overall survival for sorafenib vs placebo was 0.69 (95% confidence interval: 0.55-0.87; p = .0006), representing a 44% improvement in overall survival for sorafenib vs placebo. This result met early stopping criteria for the trial. The median overall survival duration was nearly 3 months longer for patients treated with sorafenib (10.7 months for sorafenib vs 7.9 months for placebo; p < .001).
The trial also found overall good tolerability for patients. Diarrhea was the most frequent side effect, followed by hand and foot skin reactions and then fatigue.
For patients with multifocal HCC and advanced liver disease, sorafenib has been found to be safe. However, very advanced HCC (Barcelona Clinic Liver Cancer stage D) and end-stage liver disease (Child-Pugh Class C) patients have a limited life expectancy despite treatment, which is likely attributable to their severe underlying liver dysfunction.
Sorafenib is not on the VA National Formulary. However, it may be available at local facilities on a nonformulary (case-by-case) basis, with local restrictions.