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

Based on x-ray crystallography and kinetic interaction studies, lenvatinib binds to the adenosine 5′-triphosphate binding site of VEGFR2 and to a neighbouring region via a cyclopropane ring and thereby inhibits tyrosine kinase activity and associated signalling pathways.

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.

Differentiated thyroid cancer (DTC): The recommended dosage is 24 mg orally once daily.

Renal cell carcinoma (RCC): The recommended dosage is 18 mg orally once daily with everolimus 5 mg orally once daily.

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.

None

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.

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.

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.

Hypertension: Control blood pressure prior to treatment and monitor during treatment. Withhold for Grade 3 hypertension despite optimal antihypertensive therapy. Discontinue for Grade 4 hypertension.

Cardiac Dysfunction: Monitor for clinical symptoms or signs of cardiac dysfunction. Withhold or discontinue for Grade 3 cardiac dysfunction. Discontinue for Grade 4 cardiac dysfunction.

Arterial Thromboembolic Events: Discontinue following an arterial thromboembolic event.

Hepatotoxicity: Monitor liver function prior to treatment and periodically during treatment. Withhold or discontinue for Grade 3 or 4 hepatotoxicity. Discontinue for hepatic failure.

Renal Failure or Impairment: Withhold or discontinue for Grade 3 or 4 renal failure or impairment.

Proteinuria: Monitor for proteinuria prior to treatment and periodically
during treatment. Withhold for 2 or more grams of proteinuria per 24
hours. Discontinue for nephrotic syndrome.

Diarrhea: May be severe and recurrent. Promptly initiate management for severe diarrhea. Withhold or discontinue based on severity.

Fistula Formation and Gastrointestinal Perforation: Discontinue in patients who develop Grade 3 or 4 fistula or any Grade gastrointestinal perforation.

QT Interval Prolongation: Monitor and correct electrolyte abnormalities. Withhold for QT interval greater than 500 ms or for 60 ms or greater increase in baseline QT interval.

Hypocalcemia: Monitor blood calcium levels at least monthly and replace calcium as necessary. Withhold or discontinue based on severity

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Withhold for RPLS until fully resolved or discontinue.

Hemorrhagic Events: Withhold or discontinue based on severity.

Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction: Monitor thyroid function prior to treatment and monthly during treatment.

Wound Healing Complications: Withhold lenvatinib before surgery.
Discontinue in patients with wound healing complications.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception.

Store at 25°C; excursions permitted to 15-30°C