Sorafenib OS Advantage In Advanced HCC May Depend On Hepatitis Viral Status

Viral status may be linked to sorafenib efficacy in patients with advanced inoperable hepatocellular carcinoma

medwireNews: A meta-analysis indicates that the overall survival (OS) gain achieved with sorafenib versus other tyrosine kinase inhibitors for the treatment of unresectable advanced hepatocellular carcinoma (aHCC) may be restricted to patients with only the hepatitis C virus (HCV).

The study “demonstrates that the effect of sorafenib compared with other treatments for patients with aHCC cannot be considered independent of a patient’s HBV [hepatitis B virus] and HCV status”, the authors write in the Journal of Clinical Oncology.

Philip Johnson, from the University of Liverpool, UK, and co-workers collated information from participants of three large phase III clinical trials comparing brivanib (n=577), sunitinib (n=526) or linifanib (n=510) with sorafenib (n=1643).

For patients who were HCV-positive but HBV-negative, sorafenib was associated with a significant OS benefit, with a log hazard ratio of –0.26 compared with another treatment. Median unadjusted survival was 12.6 months and 10.2 months, respectively.

However, there was no difference in OS with sorafenib versus another agent when assessing subgroups of patients who were HCV-negative but HBV-positive, or who were positive for both or neither of the viruses.

“This result is consistent across all sources of data and there is no evidence of heterogeneity”, the researchers say.

Philip Johnson et al explain that the OS advantage with HCV infection may be linked to earlier hypotheses that sorafenib may directly affect HCV viral replication, upregulate the C-RAF target of sorafenib or influence HCC cell sensitivity to the agent.

Regardless, the team recommends: “Irrespective of the mechanism, our data suggest that in future trials in aHCC, particularly where sorafenib is the control arm, there should be stratification according to etiology.”


Jackson R, Psarelli E-E, Berhane S, et al. Impact of viral status on survival in patients receiving sorafenib for advanced hepatocellular cancer: A meta-analysis of randomized phase III trials. J Clin Oncol; Advance online publication 3 January 2017. DOI: 10.1200/JCO.2016.69.5197

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