Lenvatinib

LENVIMA is a kinase inhibitor that is indicated: Differentiated Thyroid Cancer For the treatment of adult patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC). Renal Cell Carcinoma In combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). In combination with belzutifan, for the treatment of adult patients with advanced renal cell carcinoma with a clear cell component (ccRCC) following a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. In combination with everolimus, for the treatment of adult patients with advanced RCC following one prior anti-angiogenic 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 (PDGFRA), KIT, and RET. Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2 alpha (FRS2) phosphorylation.

Single Agent Therapy: DTC: The recommended dosage is 24 mg orally once daily. HCC: The recommended dosage is based on actual body weight: 12 mg orally once daily for patients greater than or equal to 60 kg or 8 mg orally once daily for patients less than 60 kg. Combination Therapy: EC: The recommended dosage is 20 mg orally once daily in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph. RCC: The recommended dosage is: 20 mg orally once daily with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph. 20 mg orally once daily with belzutifan. 18 mg orally once daily with everolimus 5 mg orally once daily. Modify the recommended daily dose for patients with renal or hepatic impairment.

None. None.

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: Consider assessment of baseline left ventricular ejection fraction (LVEF). Monitor for symptoms or signs of heart failure and, if present, assess LVEF. Withhold, reduce dose, or permanently discontinue LENVIMA based on severity. 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.

The following adverse reactions are discussed elsewhere in the labeling: Hypertension Cardiac Dysfunction Arterial Thromboembolic Events Hepatotoxicity Renal Failure and Impairment Proteinuria Diarrhea Fistula Formation and Gastrointestinal Perforation QTc Interval Prolongation Hypocalcemia Reversible Posterior Leukoencephalopathy Syndrome Hemorrhagic Events Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction Impaired Wound Healing Osteonecrosis of the Jaw (ONJ) Most common adverse reactions are: LENVIMA as single agent DTC (incidence ≥30%) hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, decreased weight, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, and dysphonia.

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

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).