• Assess BP prior to and after 1 wk, then every 2 wk for first 2 mo, and then at least monthly thereafter during therapy. Initiate or adjust medication management to control BP. Hold lenvatinib for Grade 3 hypertension that persists despite antihypertensive therapy. Resume at a reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) when hypertension is controlled or ≤Grade 2). Discontinue lenvatinib for life-threatening hypertension.
• Monitor for clinical signs and symptoms of cardiac dysfunction (shortness of breath, swollen ankles) during therapy. Hold lenvatinib for Grade 3 cardiac dysfunction until improved to Grade 0 or 1 or baseline. Resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) or discontinue depending on severity and persistence of cardiac dysfunction.
• Monitor for signs and symptoms of arterial thromboembolic events (chest pain, acute neurologic symptoms of MI or stroke) during therapy. Discontinue lenvatinib if event occurs.
• Assess for signs and symptoms of gastrointestinal perforation or fistula formation (severe abdominal pain) during therapy. Discontinue lenvatinib if gastrointestinal perforation or fistula occurs.
• Monitor ECG for patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those taking drugs known to prolong QT interval. Hold lenvatinib for development of QT interval prolongation >500 msec or >60 msec increase from baseline. Hold until improves to ≤480 msec or baseline. Resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) when QT prolongation resolves to Grade 0 or 1.
• Monitor for signs and symptoms of RPLS (severe headache, seizures, weakness, confusion, blindness or change in vision) during therapy. If symptoms occur, confirm diagnosis with MRI. Hold lenvatinib for RPLS until fully resolved. Resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) or discontinue depending on severity and persistence of neurologic symptoms.
• Monitor for bleeding (severe and persistent nose bleeds, vomiting blood, red or black stools, coughing up blood or blood clots, heavy or new onset vaginal bleeding) during therapy. Hold lenvatinib for Grade 3 hemorrhage until resolved to Grade 0 or 1. Resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) or discontinue depending on severity and persistence of hemorrhage. Discontinue lenvatinib if Grade 4 hemorrhage occurs.
• Obtain an oral exam prior to and periodically during therapy. Hold lenvatinib for at least 1 wk before scheduled dental surgery or invasive dental procedures, if possible. Discontinuation of bisphosphonate therapy may reduce the risk of ONJ. Hold lenvatinib if ONJ develops and restart after adequate resolution.

Lab Test Considerations:

• Verify negative pregnancy test before starting therapy.For the pMMR/not MSI-H advanced endometrial carcinoma indication, select patients for therapy with lenvatinib in combination with pembrolizumab based on MSI or MMR status in tumor specimens. Information on FDA-approved tests for patient selection is available at: http://www.fda.gov/CompanionDiagnostics. An FDA-approved test for selection of patients who are not MSI-H is not currently available.Monitor serum ALT and AST levels for hepatotoxicity prior to and every 2 wk for first 2 mo, and at least monthly thereafter during therapy. Hold lenvatinib for Grade 3 cardiac dysfunction until improved to Grade 0 or 1 or baseline. Resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) or discontinue depending on severity and persistence of hepatotoxicity. May cause hypoalbuminemia, ↑ alkaline phosphatase, and hyperbilirubinemia.
  • Monitor for proteinuria prior to and periodically during therapy. If urine dipstick proteinuria ≥2+ is detected, obtain 24 hr urine protein. Hold lenvatinib for ≥2 g proteinuria/24 hr and resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) when proteinuria <2 g/24 hr. Discontinue lenvatinib for nephrotic syndrome.
  • Monitor BUN and serum creatinine prior to and periodically during therapy. Hold lenvatinib for Grade 3 or 4 renal failure/impairment until resolved to Grade 0 or 1 or baseline. Resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) or discontinue depending on severity and persistence of renal impairment.
  • Monitor and correct electrolyte abnormalities. Monitor serum calcium levels at least monthly and replace calcium as needed during therapy. Interrupt and adjust lenvatinib dose based on severity, presence of ECG changes, and persistence of hypocalcemia. May cause hypokalemia, hypomagnesemia, hypoglycemia, hypercalcemia, and hyperkalemia.
  • Monitor TSH levels monthly and adjust thyroid replacement medication as needed in patients with ↓ thyroid levels.
  • May cause ↑ serum lipase and amylase, hypercholesterolemia, and ↓ platelet count.