Eisai Co., Ltd. announced that the results of a Phase III study (REFLECT study, Study 304) of its in-house discovered and developed anticancer agent lenvatinib mesylate (product names: Lenvima/Kisplyx, “lenvatinib”) in patients with hepatocellular carcinoma (HCC) have been published in the online version of The Lancet, which is one of the world’s most prestigious medical journals and was recently ranked second in the world in terms of Impact Factor. (Lead author: Professor and Chairman Masatoshi Kudo of Kindai University Faculty of Medicine, Title of paper: “Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial”).
The REFLECT study reported on in the paper was a multicenter, open-label, randomized, global Phase III study comparing the efficacy and safety of lenvatinib versus sorafenib, a standard treatment for advanced hepatocellular carcinoma, as a first-line treatment in patients with unresectable HCC. In this study, lenvatinib demonstrated a treatment effect on the primary endpoint of Overall Survival (OS) by statistical confirmation of non-inferiority to sorafenib. Additionally, lenvatinib showed highly statistically significant and clinically meaningful improvements in the secondary endpoints of Progression Free Survival (PFS), Time To Progression (TTP), and Objective Response Rate (ORR).
The paper also reported on the results of an exploratory analysis of the secondary endpoints based on blinded independent imaging review (IIR). The IIR based on both RECIST1.1, which uses the traditional assessment of the effect on change in tumor diameter, and mRECIST, which takes into account areas of tumor necrosis in addition to the RECIST 1.1 criteria, confirmed similar findings to the investigators’ review (per mRECIST criteria) of extensions in PFS and TTP as well as an increase in ORR compared to sorafenib based on lenvatinib’s superior reduction in tumor size.
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 safety profile of lenvatinib.
Eisai has submitted applications for lenvatinib for the treatment of HCC in Japan (June 2017), the United States and Europe (July 2017), China (October 2017), Taiwan (December 2017) and other countries. Eisai remains committed to providing additional clinical evidence for lenvatinib aimed at maximizing the value of the drug to patients as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.
Filed Under: Drug Discovery