NEW DRUG: LENVIMA Company: Eisai Approval Status: Approved February 2015 Specific Treatments: Differentiated thyroid cancer (DTC) Therapeutic Areas: Oncology
Lenvima tablet was approved by FDA based on a multicenter, randomized, double-blind, placebo-controlled trial in 392 patients with locally recurrent or metastatic radioactive iodine-refractory differentiated thyroid cancer and radiographic evidence of disease progression within 12 months prior to randomization, confirmed by independent radiologic review.
The subjects received LENVIMA 24 mg once daily (n=261) or placebo (n=131) until disease progression. Continue LENVIMA until disease progression or until unacceptable toxicity occurs.
Lenvima is specifically indicated for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer.
Lenvima (lenvatinib) is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.
A single 32 mg dose (1.3 times the recommended daily dose) of lenvatinib did not prolong the QT/QTc interval in a thorough QT study in healthy subjects. However, QT prolongation was observed.
After oral administration of LENVIMA, time to peak plasma concentration (Tmax) typically occurred from 1 to 4 hours post-dose. Administration with food did not affect the extent of absorption, but decreased the rate of absorption and delayed the median Tmax from 2 hours to 4 hours
In vitro binding of lenvatinib to human plasma proteins ranged from 98% to 99% (0.3 – 30 μg/mL). In vitro, the lenvatinib blood-to-plasma concentration ratio ranged from 0.589 to 0.608 (0.1 – 10 μg/mL).
Plasma concentrations declined bi-exponentially following Cmax. The terminal elimination half-life of lenvatinib was approximately 28 hours. Metabolism: CYP3A is one of the main metabolic enzymes of lenvatinib.
Excretion: Ten days after a single administration of radiolabeled lenvatinib to 6 patients with solid tumors, approximately 64% and 25% of the radiolabel were eliminated in the feces and urine, respectively.
No dose adjustment of LENVIMA is recommended when co-administered with CYP3A, Pglycoprotein (P-gp), and breast cancer resistance protein (BCRP) inhibitors and CYP3A and P-gp inducers
Effect of Lenvatinib on Other Drugs CYP3A4 or CYP2C8 Substrates: There is no projected significant drug-drug interaction risk between lenvatinib and midazolam (a CYP3A4 substrate) or repaglinide (a CYP2C8 substrate).
Information by : Ms. Sahitya Kurapati