The trial achieved its primary endpoint by meeting the statistical criteria for non-inferiority of overall survival with lenvatinib compared to sorafenib, the current standard of care for systemic treatment in this setting.
Eisai plans to present the results of this study at an upcoming medical meeting and discuss these data with regulatory authorities in the United States and worldwide.
Clinically meaningful and statistically significant improvements for lenvatinib were achieved in progression-free survival, time to progression and objective response rate, the secondary efficacy endpoints. In this study, the five most common adverse events observed in the lenvatinib arm were hypertension, diarrhea, decreased appetite, weight loss, and fatigue, which is consistent with the known side-effect profile of lenvatinib.
Analyses of the remaining secondary endpoints of quality of life and plasma pharmacokinetics parameters, as well as safety, are ongoing.
Alton Kremer, MD, PhD, Chief Clinical Officer and Chief Medical Officer, Oncology Business Group at Eisai, said: "Although much progress has been made in cancer research, there remains a great need for more options in the treatment of unresectable hepatocellular carcinoma.
"The findings from this Phase 3 trial represent an important development for previously untreated patients with unresectable hepatocellular carcinoma who unfortunately face a poor prognosis."
Lenvatinib is approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer, and in combination with everolimus for patients with advanced renal cell carcinoma who were previously treated with an anti-angiogenic therapy.
Lenvatinib is under investigation for unresectable hepatocellular carcinoma and the safety or effectiveness of the product for that use has not been established.
This international, multicenter, randomized, open-label, non-inferiority Phase 3 trial enrolled 954 patients with unresectable HCC who had not received prior systemic therapy.
Patients were randomized to receive lenvatinib 12 mg or 8 mg once a day depending on body weight (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity.
HCC is the most common type of liver cancer, accounting for about 90% of cases of primary liver cancer in the United States.
The rates of liver cancer and intrahepatic bile duct cancer have been rising steadily over the past decade, and more than 39,000 cases will be diagnosed in the United States this year. The liver cancer mortality rate has also been rising, with more than 27,000 deaths due to the disease estimated in 2016.
About Lenvima (lenvatinib)
Lenvima (lenvatinib) is a kinase inhibitor that is indicated for:
- Differentiated Thyroid Cancer (DTC): single agent for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC.
- Renal Cell Cancer (RCC): in combination with everolimus for patients with advanced RCC following one prior anti-angiogenic therapy.
Lenvatinib, discovered and developed by Eisai, is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1-3.
Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.
The combination of lenvatinib and everolimus showed increased anti-angiogenic and anti-tumor activity as demonstrated by decreased human endothelial cell proliferation, tube formation, and VEGF signaling in vitro and tumor volume in mouse xenograft models of human renal cell cancer greater than each drug alone.