SAN FRANCISCO—Although preliminary data had suggested everolimus may provide benefit for patients with advanced hepatocellular carcinoma (HCC) following sorafenib failure—for whom no treatment options currently exist—data from the phase 3 EVOLVE-1 trial reported at the 2014 Gastrointestinal Cancers Symposium showed no improvement in overall survival (OS).

Andrew X. Zhu, MD, PhD, of the Departments of Hematology/Oncology and Medicine at Massachusetts General Hospital, Boston, MA and colleagues enrolled 546 patients from 18 countries from April 2010 to March 2012 with Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC and Child-Pugh A liver function with disease that had progressed during or after sorafenib or were sorafenib-intolerant.

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Patients were randomly assigned 2:1 to everolimus 7.5 mg/day (n=362) or placebo (n=184), and all received best supportive care. CT/MRI was performed every 6 weeks. Stratification was by region (Asia vs. the rest of the world) and whether patients had macrovascular invasion.

Median age of the patients was 66 years; 84.8% were male; 86.3% had BCLC stage C disease; 16.7% were from Asia; 32.8% had macrovascular invasion; and 74% had extrahepatic disease. Prior sorafenib was discontinued for disease progression in 80.8% of patients and intolerance in 19%. Final analysis was performed when 454 deaths occurred.

Median OS, the primary endpoint, was 7.65 months for patients treated with everolimus and 7.33 months for the placebo arm (hazard ratio [HR], 1.05; 95% CI: 0.86-1.27; P = 0.675). Median time to progression was 2.96 months and 2.60 months, respectively (HR, 0.93; 95% CI: 0.75-1.15). Disease control rate was 56.1% in the everolimus arm compared with 45.1% in the placebo arm (P = 0.010).

The safety profile was consistent with that previously observed with everolimus. The most common grade 3/4 adverse events with everolimus compared with placebo were anemia (7.8% vs. 3.3%), asthenia (7.8% vs. 5.5%), decreased appetite (6.1% vs. 0.5%), and hepatitis B viral load increase or reappearance (6.1% vs. 4.4%).

No patients experienced a hepatitis C virus flare. Hepatitis B virus reactivation was experienced by 39 patients, 29 in the everolimus arm and 10 in the placebo arm. All cases were asymptomatic; however, three patients in the everolimus arm discontinued therapy.

The 2014 Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association (AGA) Institute, the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Surgical Oncology (SSO).


  1. Zhu AX, Kudo M, Assenat E, et al. Abstract 172. Presented at: 2014 Gastrointestinal Cancers Symposium. Jan. 16-18, 2014; San Francisco.