Lenvatinib Mesylate Approved in Japan for Unresectable HCC
On March 23, the multiple-receptor tyrosine kinase inhibitor lenvatinib mesylate (Lenvima) was approved in Japan for unresectable hepatocellular carcinoma (HCC). This is the first approval worldwide of lenvatinib mesylate for the indication of unresectable HCC and the first new systemic therapy to be approved in Japan for the front-line treatment of HCC in approximately 10 years.
Additionally, this is the first regulatory approval for lenvatinib mesylate under the global strategic collaboration agreement executed in March 2018 between Eisai and Merck for the codevelopment and cocommercialization of lenvatinib mesylate.
REFLECT Trial
This approval was based on a phase III clinical trial (Study 304/REFLECT) conducted by Eisai investigating lenvatinib mesylate as a first-line treatment in patients with unresectable HCC. In this study, lenvatinib mesylate demonstrated statistically significant noninferiority of overall survival (13.6 months) compared to sorafenib (12.3 months), with a hazard ratio (HR) of 0.92 (95% confidence interval [CI] = 0.79–1.06).
Additionally, lenvatinib mesylate showed highly statistically significant and clinically meaningful improvements compared to sorafenib in the secondary endpoints of progression-free survival (HR = 0.66, 95% CI = 0.57–0.77, P < .00001), time to progression (HR = 0.63, 95% CI = 0.53–0.73, P < .00001), and objective response rate (24% for lenvatinib mesylate vs 9% for sorafenib, P < .00001). Furthermore, lenvatinib mesylate helped to delay deterioration in several quality-of-life and symptom domains (prespecified secondary endpoint), including in areas such as pain and diarrhea, compared to sorafenib (nominal P value < .05).
In this study, the five most common adverse events observed in the lenvatinib mesylate arm were hypertension (42%), diarrhea (39%), decreased appetite (34%), weight loss (31%), and fatigue (30%). These findings were consistent with the known safety profile of lenvatinib mesylate.
Liver cancer is the second leading cause of cancer-related deaths, with approximately 750,000 deaths per year estimated globally. Additionally, approximately 780,000 cases are newly diagnosed each year, about 80% of which occur in Asia, including Japan and China.
HCC is the primary diagnosis in 85% to 90% of liver cancer cases. It is estimated that there are approximately 42,000 HCC patients in Japan, with approximately 26,000 deaths every year. To date, treatment options for unresectable HCC have been limited, and the prognosis is poor, emphasizing that this is an area of high unmet medical need.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
