Sorafenib significantly increases overall survival in Asian-Pacific patients with advanced hepatocellular carcinoma—a group where surgical treatments can be limited—according to findings of a phase III trial reported in an Article published early Online and in the January edition of The Lancet Oncology.
Hepatocellular carcinoma is the third most common cause of cancer-related death and is a particular challenge in the Asia-Pacific region, where 75% of cases occur. Hepatocellular carcinoma is associated with chronic infection with hepatitis B virus (HBV), which is highly prevalent in this part of the world. If patients present with single tumours and with good liver function, surgery is often successful, with around 70% of patients surviving for 5 years. Unfortunately, many patients are diagnosed when their disease is more advanced, making surgery an option in only a fifth of patients. Systemic agents that can increase survival are therefore needed.
The safety and efficacy of one such agent, sorafenib, an oral multikinase inhibitor that has anti-angiogenic and anti-proliferative properties, has already been shown earlier this year in a phase III trial in patients with hepatocellular carcinoma from Europe and North America—the Sorafenib Hepatocellular carcinoma Assessment Randomised Protocol (SHARP) trial.1 As a result of this trial, sorafenib was approved by the US Food and Drug Administration (FDA) and by the European Medicines Agency (EMEA) for the treatment of advanced hepatocellular carcinoma. However, regulatory approval in China could not be considered without evidence from a parallel study in patients from the Asia-Pacific region, who have a very different incidence of HBV infection compared with the SHARP trial population (73% vs 12%).
Ann-Lii Cheng (National Taiwan University Hospital) and colleagues therefore assessed the efficacy and safety of sorafenib in 226 patients from 23 centres in China, South Korea, and Taiwan in a randomised, double-blind, placebo-controlled phase III trial. 150 patients received 400 mg dose of oral sorafenib twice daily in 6-week cycles and 76 patients received placebo. Patients in the treatment group had a median overall survival of 6.5 months (95% CI 5.56-7.56) compared with 4.2 months (95% CI 3.75-5.46) in the placebo group—a significant difference. Sorafenib treatment also prolonged significantly the time to progression and disease control rate.
Sorafenib treatment was generally well tolerated, but patients did have some adverse side-effects; around 10% had a grade 3 or 4 skin reaction on the hands and feet, 6% had grade 3 or 4 diarrhoea, and 3% had grade 3 or 4 fatigue.
"Although other studies suggest that sorafenib might be less efficacious in patients with HBV, we do not agree with these conclusions, and believe that the large proportion of patients with HBV enrolled in our study supports the efficacy of sorafenib in this important patient subset", commented Dr Cheng.
Dr Ann-Lii Cheng, National Taiwan University Hospital, No 7, Chung-Shan South Road, Taipei, Taiwan. Email: alcheng@ntu.edu.tw Tel: +886-928-606605
Full Article: http://press.thelancet.com/TLOchengfinal.pdf
1. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359:378-90.
Notes for editors
The study design used a 2:1 drug:placebo randomisation method to ensure that the maximum number of patients received the active drug, while still allowing confirmation of the efficacy of sorafenib in the Asia-Pacific population using a placebo comparator group.
Analysis of the cost-effectiveness of sorafenib in the USA has shown that the drug is cost-effective compared with standard supportive care for liver cancer.
Journal
The Lancet Oncology