Liver Cancer Drug Lenvima Succeeds in Phase 3 Trial

RTK inhibitor demonstrates noninferiority to sorafenib

A phase 3 clinical study of the anticancer agent lenvatinib mesylate (Lenvima, Eisai) compared with sorafenib (Nexavar, Bayer) as a first-line treatment for patients with unresectable hepatocellular carcinoma has achieved its primary endpoint with the goal of demonstrating noninferiority.

Lenvatinib is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor receptors 1–3 and fibroblast growth factor receptors 1–4 in addition to other proangiogenic and oncogenic pathway-related RTKs (including platelet-derived growth factor receptor-alpha; KIT; and RET) involved in tumor proliferation.

The phase 3, global, open-label, randomized study compared the efficacy and safety of lenvatinib with that of sorafenib, a standard treatment for patients with advanced hepatocellular carcinoma, as a first-line treatment for patients with that disease. A total of 954 patients were randomly assigned to receive lenvatinib 8 mg or 12 mg once daily, depending on baseline body weight (n = 478) or sorafenib 400 mg twice daily (n = 476). Treatment was continued until disease progression or unacceptable toxicity occurred. The study’s primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), the time to progression (TTP), and the objective response rate (ORR).

Lenvatinib met the statistical criteria for noninferiority of OS compared with sorafenib and showed statistically significant and clinically meaningful improvement in PFS, TTP, and ORR. The five most common adverse events observed in the lenvatinib arm were hypertension, diarrhea, decreased appetite, weight loss, and fatigue. Analyses of the remaining secondary endpoints of quality of life and plasma pharmacokinetic parameters as well as safety are ongoing.

Liver cancer is the second-leading cause of cancer deaths, with approximately 800,000 new cases diagnosed each year throughout the world. It is estimated to be the cause of approximately 700,000 deaths per year. Hepatocellular carcinoma accounts for 85% to 90% of primary liver cancer cases. Hepatocellular carcinoma is associated with chronic liver disease, in particular cirrhosis. Major causes of cirrhosis include infection with hepatitis B virus or hepatitis C virus. However, according to a recent investigation, non-B/non-C hepatocellular carcinoma is on the rise.

Surgery is the first option for treatment. However, in many cases of recurrence after resection or when the cancer is deemed advanced at diagnosis, surgery is not applicable because the disease has already metastasized. Currently, the only drug approved for systemic therapy of unresectable hepatocellular carcinoma is sorafenib.

Source: Eisai; January 25, 2017.