Adding everolimus to sorafenib was not found to improve efficacy compared with sorafenib alone and was more toxic in patients with unresectable or metastatic hepatocellular carcinoma (HCC), a study published in the journal Annals of Oncology has shown.1

The multikinase inhibitor sorafenib is the standard of care for frontline systemic treatment of advanced HCC. Preclinical data have suggested that the addition of everolimus, an mTOR inhibitor, to sorafenib may have additive effects compared with single-agent sorafenib.

For the international phase 2 trial, researchers enrolled 106 patients with unresectable to metastatic HCC who had a Child-Pugh liver dysfunction score of 7 or less. Patients were randomly assigned to receive sorafenib 800 mg orally daily alone or with everolimus 5 mg orally daily until disease progression or unacceptable toxicity.

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Results showed that the 12-month progression-free survival rate was 70% (95% CI, 54 – 83) with sorafenib monotherapy compared with 68% (95% CI, 53 – 81) with sorafenib and everolimus. The response rate per RECIST criteria was 0% and 10%, respectively; 23% and 35%, respectively, using modified RECIST criteria.

Researchers found that median progression-free survival was 6.6 months for sorafenib alone vs 5.7 months for the combination arm. Overall survival was 10 months and 12 months, respectively. Time to progression and duration of disease stabilization were also similar between the 2 treatment arms.

In regard to safety, grade 3 or 4 adverse events were more frequently associated with sorafenib plus everolimus (88%) than sorafenib alone (72%).

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Quality of life scores were similar between the 2 groups over time, but researchers observed a greater worsening in physical well-being and mood in the combination arm.

The findings suggest that further testing of this combination in molecularly unselected patients with HCC does not seem to be warranted.


  1. Koerberle D, Dufour J-F, Demeter G, et al. Sorafenib with or without everolimus in patients with advanced hepatocellular carcinoma (HCC): a randomized multicenter, multinational phase II trial (SAKK 77/08 and SASL 29) [published online ahead of print February 15, 2016]. Ann Oncol. doi: 10.1093/annonc/mdw054.