LENVACENT-10

Lenvatinib is a kinase inhibitor that is indicated:

• For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC).
• In combination with everolimus, for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior antiangiogenic therapy.
• For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC).

Targeted Cancer Therapy

Lenvatinib is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib inhibits other kinases 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; platelet-derived growth factor receptor alpha (PDGFR ), KIT, and RET. Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with concurrent inhibition of FGF-receptor substrate 2 (FRS2 ) phosphorylation. Absorption: The time to peak plasma concentration (Tmax) typically occurred from 1 to 4 hours post-dose. Administration with a high-fat meal (approximately 900 calories of which approximately 55% were from fat, 15% from protein, and 30% from carbohydrates) did not affect the extent of absorption, but decreased the rate of absorption and delayed the median Tmax from 2 hours to 4 hours. Distribution: In vitro binding of Lenvatinib to human plasma proteins ranged from 98% to 99% at concentrations of 0.3 to 30 μg/mL. The blood-to-plasma concentration ratio ranged from 0.59 to 0.61 at concentrations of 0.1 to 10 μg/mL in vitro. Metabolism: The main metabolic pathways for Lenvatinib in humans were identified as enzymatic (CYP3A and aldehyde oxidase) and non-enzymatic processes. Excretion: Ten days after a single administration of radiolabeled Lenvatinib, approximately 64% and 25% of the radiolabel were eliminated in the feces and urine, respectively. Elimination: The terminal elimination half-life of Lenvatinib was approximately 28 hours.

• Differentiated thyroid cancer (DTC): The recommended dosage is 24 mg orally once daily.
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• Renal cell carcinoma (RCC): The recommended dosage is 18 mg orally once daily with everolimus 5 mg orally once daily.
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• Hepatocellular carcinoma (HCC): The recommended dosage is based on actual body weight:
• 12 mg orally once daily for patients greater than or equal to 60 kg
• 8 mg orally once daily for patients less than 60 kg.
• Modify the recommended daily dose for certain patients with renal or hepatic impairment.

Drugs That Prolong the QT Interval: Lenvatinib has been reported to prolong the QT/QTc interval. Avoid coadministration of Lenvatinib with medicinal products with a known potential to prolong the QT/QTc interval.

Not specified

• In DTC, the most common adverse reactions (incidence ≥30%) for lenvatinib are hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, decreased weight, nausea, stomatitis, headache, vomiting, proteinuria, palmarplantar erythrodysesthesia syndrome, abdominal pain, and dysphonia.
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• In RCC, the most common adverse reactions (incidence ≥30%) for lenvatinib and everolimus are diarrhea, fatigue, arthralgia/myalgia, decreased appetite, vomiting, nausea, stomatitis/oral inflammation, hypertension, peripheral edema, cough, abdominal pain, dyspnea, rash, decreased weight, hemorrhagic events, and proteinuria.
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• In HCC, the most common adverse reactions (incidence ≥20%) for lenvatinib are hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism, and nausea.

• Lactation: Advise not to breastfeed.

Due to the high plasma protein binding, Lenvatinib is not expected to be dialyzable. Death due to multiorgan dysfunction occurred in a patient who received a single dose of Lenvatinib 120 mg orally.

Store below 30°C in a dry place. Protect from light. Keep out of the reach of children.

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