Aside from the multikinase inhibitor sorafenib, there are no effective systemic therapies for the treatment of advanced hepatocellular carcinoma.
Dr Andrew Zhu and colleagues assessed the efficacy of everolimus in patients with advanced hepatocellular carcinoma for whom sorafenib treatment failed.
EVOLVE-1 was a randomized, double-blind, phase 3 study conducted among 546 adults with Barcelona Clinic Liver Cancer stage B or C hepatocellular carcinoma and Child-Pugh A liver function whose disease progressed during or after sorafenib or who were intolerant of sorafenib.
The team enrolled patients from 17 countries between 2010 and 2012.
Randomization was stratified by region and macrovascular invasion.
|Hepatitis B viral reactivation was experienced by 39 patients|
|Journal of the American Medical Association|
Everolimus, 7.5 mg/d, or matching placebo, both given in combination with best supportive care and continued until disease progression or intolerable toxicity.
Per the 2:1 randomization scheme, 362 patients were randomized to the everolimus group and 184 patients to the placebo group.
The team's primary end point was overall survival.
The research team's secondary end points included time to progression and the disease control rate.
The team noted no significant difference in overall survival between treatment groups, with 84% of deaths in the everolimus group, and 82% of deaths in the placebo group.
Median time to progression with everolimus and placebo was 3 months, and 2.6 months, respectively.
The team found that disease control rate was 56% and 45%, respectively.
The researchers noted that the most common grade 3/4 adverse events for everolimus vs placebo were anemia, asthenia, and decreased appetite.
No patients experienced hepatitis C viral flare.
Based on central laboratory results, hepatitis B viral reactivation was experienced by 39 patients.
All cases were asymptomatic, but 3 everolimus recipients discontinued therapy.
Dr Zhu's team concludes, "Everolimus did not improve overall survival in patients with advanced hepatocellular carcinoma whose disease progressed during or after receiving sorafenib or who were intolerant of sorafenib."