In short
Lenvatinib mesilate is a targeted cancer medicine known as a kinase inhibitor. It is authorised for use in the EU and is being studied in clinical trials for conditions including advanced kidney cancer. Registry data show two active trials investigating lenvatinib, with one Phase 3 study enrolling 500 participants.
Key points
- Lenvatinib is an oral multi-receptor tyrosine kinase inhibitor that blocks signals involved in tumour growth.
- It is authorised as a medicine in the EU for several cancer types, including thyroid, kidney, liver and endometrial cancers.
- A Phase 3 trial is comparing immunotherapy combinations followed by lenvatinib in 500 people with metastatic renal cell carcinoma.
- A completed Phase 1 trial compared the bioavailability of lenvatinib capsules in 36 healthy volunteers.
- Lenvatinib is given as capsules taken by mouth.
- In trials, lenvatinib is being looked at as a test medicine and as a comparator.
What is lenvatinib mesilate?
Lenvatinib mesilate is a targeted cancer medicine belonging to a class known as kinase inhibitors. It is a chemically synthesised substance, classified under ATC codes L01EX08 and L01XE29. The medicine is also known simply as lenvatinib and is sold under the trade name LENVIMA. Lenvatinib is already authorised as a medicine in the European Union, with authorisation held by Eisai GmbH.
In the clinical trial records, lenvatinib mesilate appears as the test substance in two trials and as a comparator in one trial. This means the medicine is being investigated both as a potential treatment option and as a reference against which other treatments are measured.
How does lenvatinib mesilate work?
Lenvatinib is an oral, multi-receptor tyrosine kinase inhibitor. It blocks the activity of several proteins involved in cancer growth, including vascular endothelial growth factor (VEGF) receptors VEGFR1, VEGFR2 and VEGFR3, as well as fibroblast growth factor receptors (FGFR), platelet-derived growth factor receptors (PDGFR) alpha, KIT and RET. By inhibiting these receptors, lenvatinib interferes with signals that help tumours form new blood vessels and grow. This is how it works to slow down or stop the progression of certain cancers.
Which conditions is lenvatinib mesilate used or studied for?
Lenvatinib is authorised for use in several types of cancer. The prescribing information lists the following indications:
- Differentiated thyroid cancer – for adults with locally recurrent or metastatic, progressive, radioactive iodine-refractory disease.
- Renal cell carcinoma – for adults with advanced kidney cancer, in combination with other medicines.
- Hepatocellular carcinoma – for the first-line treatment of unresectable liver cancer.
- Endometrial carcinoma – for patients with advanced endometrial cancer that has progressed after prior systemic therapy.
The clinical trial records also list lenvatinib as being studied in metastatic renal cell carcinoma. A written request from the US Food and Drug Administration (FDA) describes planned studies of lenvatinib in children and young people with conditions including Ewing sarcoma, rhabdomyosarcoma, high-grade glioma and osteosarcoma.
How is lenvatinib mesilate given?
Lenvatinib mesilate is given as capsules that are taken by mouth. The product information describes a 10 mg hard capsule formulation. In the prescribing information, the recommended dosage for differentiated thyroid cancer is 24 mg orally once daily; for hepatocellular carcinoma it is 12 mg once daily for patients weighing 60 kg or more, or 8 mg once daily for those weighing less than 60 kg. For endometrial carcinoma and renal cell carcinoma, the recommended dosage is 20 mg orally once daily in combination with other medicines.
What do the clinical trials show?
There are two clinical trials in the registry data that involve lenvatinib mesilate. One is a Phase 1 study and one is a Phase 3 study.
What did the phase 1 trial look at?
The Phase 1 trial was a bioavailability study completed in healthy volunteers. It compared two test formulations of lenvatinib 10 mg capsules with a reference product (LENVIMA 10 mg hard capsules) under fasting and fed conditions. The study enrolled 36 participants. The primary outcome measured pharmacokinetic parameters, which describe how the drug is absorbed, distributed and eliminated by the body. These included the maximum plasma concentration (Cmax), the time to reach that maximum (tmax), the area under the plasma concentration–time curve from pre-dose to 72 hours (AUC0-72), and the half-life of the medicine.
What is the phase 3 trial studying?
The Phase 3 trial is a randomised study in people with metastatic renal cell carcinoma, a type of advanced kidney cancer that has spread to other parts of the body. It is comparing two treatment strategies: immunotherapy combinations (IO-IO) versus immunotherapy plus a tyrosine kinase inhibitor (IO-TKI), followed by a TKI such as lenvatinib at disease progression. The study plans to enrol 500 participants. Its co-primary endpoints are progression-free survival during second-line treatment (PFS-2) and overall survival (OS). PFS-2 is defined as the time from randomisation to disease progression or death during second-line treatment, while OS is the time from randomisation to death from any cause. The trial is currently authorised, meaning it has received regulatory approval to begin.
What side effects are known?
A published case report describes long-term treatment with lenvatinib in a young patient with papillary thyroid cancer who had already received three other kinase inhibitors. The report notes that lenvatinib was approved for radioiodine-refractory metastatic thyroid cancer based on a Phase 3 trial that showed longer progression-free survival in the lenvatinib arm compared with placebo. The report focuses on clinical benefit and does not provide a detailed list of side effects from this case. The prescribing information from the US includes warnings and precautions, though the specific side effect details are not fully listed in the excerpt provided.