Product Introduction :
Lenvatinib (R&D code: E7080), developed by Japan Eisai, is a multi-target receptor tyrosine kinase (RTK) inhibitor. It can inhibit VEGFR1, VEGFR2 and VEGFR3, as well as other RTKs related to pathological neovascularization, tumor growth and cancer progression, including fibroblast growth factor (FGF) receptors (FGFR1,2,3,4) and platelet-derived growth factor receptor α (PDGFRα), KIT and RET.
In 2015, Lenvatinib was approved for the treatment of aggressive, locally advanced or metastatic differentiated thyroid cancer by U.S. FDA and EMA. In 2016, lenvatinib combined with everolimus was successively approved for the treatment of advanced renal cell carcinoma by FDA and EMA.
In March 2018, lenvatinib was approved in Japan for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). This is the first time that the drug has been approved for the treatment of hepatocellular carcinoma in the world, and it is also the first innovative systemic therapy for liver cancer that can be used for front-line treatment in Japan in 10 years.
Compared with everolimus alone, lenvatinib combined with everolimus can prolong the progression-free survival (PFS) and increase the objective response rate and overall survival rate of patients in the treatment of advanced RCC. Study results showed that, the median PFS of patients in the group of lenvatinib combined with everolimus was 14.6 months, and the median PFS in the everolimus alone group was 5.5 months, the former was nearly 3 times the latter. Compared to the single agent group, the risk of progressive disease (PD) or death in the combination group was reduced by 63%. The ORRs in the combination group and the single agent group were 37% and 6%, respectively; the OSs in the combination group and the single agent group were 25.5 months and 15.4 months, respectively.
For the first-line treatment of surgically unresectable HCC, the REFLECT study of the phase III clinical trial of lenvatinib released by the American Society of Clinical Oncology (ASCO) at the 2017 annual conference showed that, in terms of the primary endpoints, the OS of the lenvatinib group was longer than that of the sorafenib group; and in terms of the secondary endpoint, the PFS of the lenvatinib group was twice that of the sorafenib group (7.4 vs 3.7 months); and the median time to progression ( mTTP) and objective response rate of the lenvatinib group were higher than those in the sorafenib group (8.9 vs 3.7 months, 24% vs 9%). The REFLECT study was a global multicenter randomized, open-label and non-inferiority (NI) clinical trial. The great success of lenvatinib in the REFLECT study may change the current status of medications in liver cancer in the past decade.
1. Hepatocellular carcinoma: for the treatment of patients with unresectable hepatocellular carcinoma (HCC);
2. Differentiated thyroid cancer: A single agent is used for the treatment of patients with locally recurrent/metastatic and progressive radioiodine refractory differentiated thyroid cancer;
3. Renal cell carcinoma: Lenvatinib combined with everolimus is used for the treatment of patients with advanced RCC who have previously received vascular endothelial growth factor targeted therapy.
Administration and Dosage :
1. For the treatment of differentiated thyroid cancer (DTC), 24 mg daily, orally, once a day;
2. For the treatment of renal cell carcinoma (RCC), 18 mg lenvatinib + 5mg everolimus, orally, once a day;
3. For the treatment of hepatocellular carcinoma (HCC), 12 mg, once a day for patients with body weight ≥60kg; and 8 mg, once a day for patients with body weight<60 kg.
Lenvatinib must be taken at the same time every day. If you forget to take the medicine and fail to take it orally within 12 hours, you should skip the dose and take the next dose at the scheduled medication time.
Lenvatinib capsules should be swallowed in a whole or dissolved in a small cup of liquid before taking. You can measure a tablespoon of water or apple juice in a glass cup and then put the capsules into the cup (the capsules need not to be opened or crushed), let the capsules in the liquid for at least 10 minutes, and stir for at least 3 minutes, then drink the liquid. After drinking, you can add the same amount (one tablespoon) of water or apple juice to the glass cup, and mix well, then drink the remaining liquid.