Lenvatinib is an oral multi-target receptor tyrosine kinase inhibitor. Its pharmacologic activity includes inhibition of VEGFR1–3, FGFR1–4, PDGFRα, KIT and RET.
Pharmacokinetics
Following oral administration, lenvatinib is absorbed and reaches peak concentrations relatively quickly. A high-fat meal does not materially change the extent of absorption, although it can delay the time to peak concentration.
Lenvatinib is highly protein bound, with reported protein binding of approximately 97–99%.
Metabolism
Human metabolism involves both enzymatic and non-enzymatic pathways. CYP3A and aldehyde oxidase contribute to metabolic clearance.
Elimination half-life
The terminal elimination half-life is approximately 28 hours according to FDA prescribing information.
Molecular targets
| Target group | Examples |
|---|---|
| VEGF receptors | VEGFR1, VEGFR2, VEGFR3 |
| FGF receptors | FGFR1, FGFR2, FGFR3, FGFR4 |
| Other RTKs | PDGFRα, KIT, RET |
Clinical evidence
In differentiated thyroid cancer, the SELECT trial evaluated lenvatinib in patients with radioactive-iodine-refractory disease. The EMA reports median progression-free survival of 18.3 months with Lenvima compared with 3.6 months with placebo in the principal study population.
For hepatocellular carcinoma, a major study enrolled 954 previously untreated patients with unresectable disease and found lenvatinib to be at least as effective as sorafenib for overall survival according to the EMA assessment.
Clinical evidence should always be interpreted in relation to the specific disease, trial population, comparator and regulatory indication.
Limitations
Clinical-trial results do not predict an individual patient’s response. Differences in disease characteristics, previous treatments, organ function and combination therapy can materially affect outcomes.