The first interim results of the GIDEON registry trial, in which patients with unresectable hepatocellular carcinoma were treated with sorafenib (Nexavar), revealed that oncologists use this treatment much differently from other specialists. Results in 479 patients indicate that oncologists were more likely to treat patients with advanced cancer, yet were also less likely than hepatologists or gastroenterologists to use a full 800-mg starting dose, and also used sorafenib for a shorter time (11.7 vs 13.1 weeks for gastroenterologists and hepatologists). The first interim results of the GIDEON study were presented in January at the Gastrointestinal Cancers Symposium in San Francisco.¹

“Hepatologists use a higher dose of sorafenib on average in patients with hepatocellular carcinoma than do medical oncologists, but this is not explained by a difference in toxicities,” said lead researcher Alan Venook, MD, Professor in the Department of Medicine at the University of California, San Francisco. “Toxicities among these patients appear to be comparable across specialties, including hand-foot syndrome and hematologic toxicities.”

Real-world Patterns

The GIDEON trial researchers aim to evaluate the use of sorafenib in real-life circumstances, and have the goal of accruing 3,000 patients from over 400 sites in 40 countries. In previous studies, treatment with sorafenib has produced a marked improvement in overall survival for patients with hepatocellular carcinoma, and it is the only systemic therapy indicated for treatment of the disease. The GIDEON trial was designed to explain differences in outcome with sorafenib seen in previous studies, ie, less favorable outcomes in Asia-Pacific regions than Western countries, where patients tend to have a lower incidence of hepatitis B and less advanced disease, Dr. Venook said.

“We designed GIDEON to look at the global use patterns of sorafenib and to give us a look at how it is used in the real-world setting. We’re hoping that the results of the trial may explain the differences in outcome we’ve seen in previous studies,” he added.

The initial results in 479 patients indicate that there are clear differences among countries as to which specialists are more likely to treat hepatocellular carcinoma, as well as their use of sorafenib. About half of patients in the United States were cared for by medical oncologists, but two-thirds of those in Europe were treated by hepatologists and gastroenterologists. On the whole, medical oncologists were more likely to treat patients with stage IV hepatocellular carcinoma and less likely to treat patients with Child-Pugh B disease than hepatologists and gastroenterologists.

In Asia, hepatologists usually used full doses of sorafenib (800 mg/d) at the start of therapy. Medical oncologists from the same region as well as those in the United States were most likely to start therapy at about 500 to 530 mg/d, however. “In the U.S., medical oncologists used the starting dose of 800 mg/d only half the time, while in the Asia-Pacific, gastroenterologists and hepatologists almost always used the full dose at the start of treatment,” Dr. Venook said. The median dose of sorafenib was also lower for treatment by medical oncologists than by hepatologists, at 570 vs 770 mg/d, he said.

Study Limitations

Dr. Venook noted that GIDEON trial was limited by the lack of specified follow-up intervals and assessments, as well as details on dose adjustments. “All of this was at the discretion of the treating physician,” he said.

Dr. Venook also acknowledged that the difference in sorafenib use patterns among physicians in the GIDEON trial may have been due to selection bias.

“However, the data do generate some questions,” he said. Differences in treatment patterns might be explained by the extent of cancer or liver dysfunction among patients as well as physician expectation or patient preferences, according to Dr. Venook. “Our hope is to mine the mature data from GIDEON to see if we can get to the bottom of why the drug is used differently among specialists,” he said. ■

Financial Disclosure: Dr. Venook reported that he has received research funding from Bayer.

Reference

1. Venook AP, Lencioni R, Marrero JA, et al: First interim results of the global investigation of therapeutic decisions in hepatocellular carcinoma (HCC) and of its treatment with sorafenib (GIDEON) study: Use of sorafenib by oncologists and nononcoloogists in the management of HCC. Gastrointestinal Cancers Symposium. Abstract 157. Presented January 21, 2011.