Sorafenib is Safe, Effective for Treating HCC in Asian Patients

ABSTRACT: Benefits were similar to those in the Western population even though the Asian patients had more advanced disease.

CHICAGO-Sorafenib (Nexavar) is safe and prolongs overall survival and time to progression in Asian patients with advanced hepatocellular carcinoma (HCC), finds the randomized phase III Asia-Pacific liver cancer study. Moreover, efficacy was similar to that in the Western population even though the Asian patients had more adverse prognostic factors.

"We are now much more comfortable to say that sorafenib is safe and efficacious in HCC patients across geographic regions."

                                   - Dr. Ann-Lii Cheng

Previous trials have shown sorafenib to be efficacious for treating advanced HCC in populations of patients drawn from Europe, the Middle East, the Americas, and Oceania, lead author Ann-Lii Cheng, MD, PhD, said at ASCO 2008 (abstract 4509).

“The reason we had to do a separate study of sorafenib in the Asia-Pacific region is because there may exist geographic differences of this cancer around the world,” he explained, citing the greater role of hepatitis B virus infection and possibly different management practices in this region.

In the trial, patients from China, Taiwan, and Korea who had advanced HCC, an ECOG score of 0 to 2, and Child-Pugh class A disease, and had not received any prior systemic therapy were stratified and randomized in 2:1 fashion to sorafenib or placebo, said Dr. Cheng, professor of internal medicine, National Taiwan University Hospital, Taipei. Analyses were based on 150 patients in the sorafenib group and 76 in the placebo group.

Longer Overall Survival

Compared with their counterparts receiving placebo, patients receiving sorafenib had significantly longer overall survival (6.5 vs 4.2 months, HR 0.68) and time to progression (2.8 vs 1.4 months, HR 0.57). According to RECIST criteria, the sorafenib group had a similar overall response rate (3% vs 1%) but a much higher rate of stable disease (54% vs 28%).

Subgroup analyses showed that the overall survival benefit was similar regardless of age, performance status, and the presence of macroscopic vascular invasion or extrahepatic spread.

The incidence of drug-related serious adverse events was 9% in the sorafenib patients and 1% in the placebo patients, Dr. Cheng reported. Patients in the sorafenib group had higher rates of grade 3-4 hand-foot skin reaction (11% vs 0%) and diarrhea (6% vs 0%).

Comparing the trial with the phase III SHARP trial of sorafenib, which had the same inclusion and exclusion criteria but was conducted in a predominantly Western population (Llovet JM et al, ASCO 2007, abstract LBA-1), Dr. Cheng noted that patients in the Asia-Pacific trial had more advanced disease-but efficacy was almost identical across the trials.

“We are now much more comfortable to say sorafenib is safe and efficacious in patients with HCC across geographic regions around the world,” he said.

 
Vantage Point

Comparing the SHARP and Asia-Pacific Trials

Median overall survival was poorer in the Asia-Pacific trial than in the SHARP trial, whether patients received sorafenib (6.5 vs 10.7 months) or placebo (4.2 vs 7.9 months), commented Dr. Llovet, of Mount Sinai School of Medicine, New York, and the University of Barcelona. He attributed this to the more advanced stage of disease in the former trial.

Another difference, he noted, was the higher rate in the Asia-Pacific trial than in the SHARP trial of hand-foot skin reaction of any grade (45% vs 21%) and specifically of grade 3-4 (11% vs 8%), which may point to ethnicity-dependent toxicity and warrants further study. Still, Dr. Llovet said, the two trials’ overall findings are consistent.

“Regarding whom we should treat, sorafenib is indicated in patients with advanced hepatocellular carcinoma, meaning symptomatic or with vascular invasion or extrahepatic spread, and in those patients progressing after loco-regional therapies, regardless of eth-nicity,” he concluded.