Sorafenib survival effect in liver cancer may depend on HCV-status

Last Updated: 2017-01-06

By Will Boggs MD

NEW YORK (Reuters Health) - Treatment with sorafenib is associated with improved overall survival in hepatitis C virus (HCV)-positive patients with hepatocellular cancer (HCC), according to a meta-analysis of clinical trials in which sorafenib was the control arm.

Patients negative for HCV did not appear to benefit, however, researchers report in the Journal of Clinical Oncology, online January 3.

"The results cannot be considered definitive," senior author Dr. Philip Johnson from the University of Liverpool, U.K., told Reuters Health by email. "Only a prospective randomized trial of sorafenib against placebo, stratified for etiology, could provide this. Nonetheless, clinicians treating patients with non-hepatitis C-related advanced HCC should realize that the effect of sorafenib is likely to be very modest in terms of overall survival, and balancing such benefit against toxicity will be the key to successful management."

Sorafenib is the current standard of care for advanced unresectable HCC, but the relationship between survival advantage and disease etiology remains unclear.

Dr. Johnson and colleagues investigated the effect of etiology, defined by patients' hepatitis B virus (HBV) and HCV status, on overall survival in their meta-analysis of patient-level data from three phase 3 clinical trials involving 3,256 patients.

Median overall survival ranged from 8.45 months to 9.67 months in the three trials. In subgroup analysis, patients positive for HCV and negative for HBV were the only group to have significant evidence that treatment with sorafenib provided better overall survival than the comparator.

There was no evidence of a beneficial effect of sorafenib on overall survival among patients who were HBV positive and HCV negative, the largest group of patients.

There was a trend supporting the use of sorafenib for patients negative for both HBV and HCV and for patients positive for both HBV and HCV, but these trends fell short of statistical significance.

"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," the researchers note.

Dr. Oliver Waidmann from Universitätsklinikum Frankfurt, Goethe-Universität, Frankfurt, Germany, who has also investigated the use of sorafenib for advanced HCC, told Reuters Health by email, "Sorafenib has been compared with other TKIs (tyrosine-kinase inhibitors) but not with best supportive care. Therefore, we cannot conclude if it is active or not in HBV-infected HCC patients compared to placebo."

"Sorafenib is still the treatment of choice in HCC patients," he concluded. "Until the expected approval of PD-1 antibody for HCC treatment, sorafenib will be the first-line treatment of choice in HCC patients not amenable to local treatment."

SOURCE: http://bit.ly/2hXFyll

J Clin Oncol 2017.