Eisai's Lenvatinib Meets Primary Endpoint in Phase 3 Carcinoma Study

Eisai Inc. announced positive topline results from the randomized, multicenter Phase 3 trial (Study 304) evaluating the company’s multiple receptor tyrosine kinase inhibitor, lenvatinib (marketed as Lenvima), for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). 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.

“Although much progress has been made in cancer research, there remains a great need for more options in the treatment of unresectable hepatocellular carcinoma,” said Alton Kremer, MD, PhD, Chief Clinical Officer and Chief Medical Officer, Oncology Business Group at Eisai. “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.