Patients with hepatocellular carcinoma and moderate liver dysfunction can derive benefit from, and be treated safely with, sorafenib (Nexavar), according to the second interim analysis of the GIDEON trial, presented at the 2011 ASCO Annual Meeting by Jorge A. Marrero, MD, of the University of Michigan in Ann Arbor.1
Real-life Practice Settings
GIDEON (Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of Its Treatment with Sorafenib) is an ongoing, global, prospective study of sorafenib in real-life practice. It is evaluating the drug in diverse settings and patient subgroups where data are limited, such as for patients with Child-Pugh B disease, who are generally excluded from liver cancer trials.
Approximately half of the 3,322 patients enrolled were eligible for the second interim safety analysis, 957 of whom were classified Child-Pugh A, 367 were Child-Pugh B, and 35 were Child-Pugh C patients. Adverse events were similar among the arms but serious events occurred in 56% of Child-Pugh B and 63% of Child-Pugh C patients, vs 29% of Child-Pugh A patients. Drug-related serious adverse events were seen in 15%, 6%, and 8%, respectively, and events resulting in permanent discontinuation of sorafenib were observed in 38% of Child-Pugh B, 51% of Child-Pugh C, and 24% of Child-Pugh A patients.
“Compared with Child-Pugh A patients, Child-Pugh B patients did not have a higher incidence of drug-related adverse events but had a higher incidence of liver-associated events. Also, as liver function worsened, there was a significant increase in the death rate,” he added, noting that most deaths were due to tumor progression or underlying liver disorders.
“Our preliminary interim analysis of results indicates that the sorafenib safety profile is generally similar in the Child-Pugh B and Child-Pugh A patients,” Dr. Marrero concluded.
While median overall survival reached 10.3 months for Child-Pugh A patients, it was 4.8 months for Child-Pugh B and just 2.0 months for Child-Pugh C patients. However, time to progression was similar for Child-Pugh B and Child-Pugh A: 3.6 and 4.2 months, respectively, vs 2.1 months for Child-Pugh C.
“The shorter median overall survival in the Child-Pugh B patients most likely reflects the poorer prognosis and natural history of liver disease in this population,” he suggested. “Consistent with previously reported studies, these preliminary data indicate that Child-Pugh status appears to be a useful prognostic factor for overall survival.”
Mean daily dose was 630 mg, which was similar among the groups, and, somewhat surprisingly, dose interruptions and modifications were also comparable. Median duration of treatment, however, was significantly shorter for Child-Pugh B: 9 weeks vs 12 weeks for Child-Pugh A, and only 4 weeks for Child-Pugh C. ■
Disclosure: Dr. Marrero reported receiving honoraria from Bayer and Onyx and research funding from Bayer.
SIDEBAR: Child-Pugh Score
Expert Point of View: Sorafenib Acceptable in Child-Pugh B Patients with Hepatocellular Carcinoma
1. Marrero JA, Lencloni R, Kudo M, et al: Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of Its Treatment with Sorafenib (GIDEON) second interim analysis in more than 1,500 patients: Clinical findings in patients with liver dysfunction. 2011 ASCO Annual Meeting. Abstract 4001. Presented June 7, 2011.
The GIDEON trial “can provide us with important information on safety and single-arm efficacy in the Child-Pugh B population,” said Bert H. O’Neil, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill.
“The results suggest that safety is similar between...
The Child-Pugh score, a prognostic measure used in patients with chronic liver disease, is determined by five clinical measures, including total bilirubin level; serum albumin level; prothrombin time expressed by international normalized ratio (INR), presence of ascites (none, mild, severe); and...