Eisai Co., Ltd. and Merck & Co., Inc., Kenilworth N.J., U.S.A., known as MSD outside of the United States and Canada, announced today that the European Commission (EC) has granted a marketing authorization for the oral receptor tyrosine kinase (RTK) inhibitor LENVIMA (lenvatinib mesylate) as a single agent for the first-line treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy. This is the first new first-line treatment option for advanced or unresectable HCC to be approved in Europe in approximately 10 years.
This approval was based on results from REFLECT (Study 304), where LENVIMA demonstrated a treatment effect on overall survival (OS)(1) by statistical confirmation of non-inferiority, as well as statistically significant superiority and clinically meaningful improvements in progression-free survival (PFS)(2) and objective response rate (ORR) (3) when compared with sorafenib in patients with previously untreated unresectable HCC.
REFLECT showed that LENVIMA achieved the primary endpoint, demonstrating a treatment effect on OS by statistical confirmation of non-inferiority to sorafenib. Patients treated with LENVIMA experienced a median OS of 13.6 months compared to 12.3 months with sorafenib (Hazard Ratio (HR): 0.92; 95% Confidence Interval (CI): 0.79-1.06). The OS analysis was conducted as prespecified in the statistical analysis plan when 351 events had occurred in the LENVIMA arm and 350 events had occurred in the sorafenib arm. Regarding secondary efficacy endpoints, according to independent imaging review based on mRECIST criteria, LENVIMA showed statistically significant superiority and clinically meaningful improvements as compared to sorafenib in median PFS: LENVIMA 7.3 months versus sorafenib 3.6 months (HR: 0.64; 95% CI: 0.55-0.75; p<0.0001) and ORR: LENVIMA 41% versus sorafenib 12% (p<0.0001).
In the EU package insert, the most frequently reported adverse reactions (occurring in >/=30% of patients) are hypertension (44.0%), diarrhoea (38.1%), decreased appetite (34.9%), fatigue (30.6%), and weight decreased (30.4%).
Liver cancer is the second leading cause of cancer-related death and is estimated to be responsible for 750,000 deaths per year globally, with 780,000 cases newly diagnosed each year.(1) HCC accounts for 85% to 90% of liver cancer cases. Treatment options for unresectable HCC are limited and the prognosis is poor, making this an area of high unmet medical need.
Currently, LENVIMA is also available under the product name Kisplyx in combination with everolimus for use in the treatment of renal cell carcinoma (second-line treatment) in Europe. LENVIMA is available for use in the treatment of thyroid cancer in over 50 countries including in Europe, Japan and the United States. In Japan, approximately 3,000 HCC patients have been treated with LENVIMA since the approval of the HCC indication in March 2018.
(1) Overall Survival (OS): The time period from the commencement of cancer treatment up until death by any cause. Whether the cause of death is cancer or not is not taken into consideration for this variable.
(2) Progression Free Survival (PFS): PFS is the objectively confirmed time from the commencement of cancer treatment to the date of disease progression, or date of death from any cause, whichever occurs first.
(3) Objective Response Rate (ORR): ORR is the combined proportion of patients whose tumor was eliminated (complete response) and whose tumor was reduced by over 30% in size (partial response) as verified by imaging assessment.