Sunitinib

SUTENT is a kinase inhibitor indicated for: • treatment of adult patients with gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate. • treatment of adult patients with advanced renal cell carcinoma (RCC). • adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy. • treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in adult patients with unresectable locally advanced or metastatic disease.

Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs), some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was evaluated for its inhibitory activity against a variety of kinases (>80 kinases) and was identified as an inhibitor of platelet-derived growth factor receptors (PDGFRα and PDGFRβ), vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). Sunitinib inhibition of the activity of these RTKs has been demonstrated in biochemical and cellular assays, and inhibition of function has been demonstrated in cell proliferation assays.

GIST and Advanced RCC: • The recommended dosage is 50 mg orally once daily for the first 4 weeks of each 6-week cycle (Schedule 4/2). Adjuvant Treatment of RCC: • The recommended dosage is 50 mg orally once daily for the first 4 weeks of a 6-week cycle (Schedule 4/2) for a maximum of 9 cycles. pNET: • The recommended dosage is 37.5 mg orally once daily.

None. None

Boxed warning (hepatotoxicity): Hepatotoxicity may be severe, and in some cases, fatal. Monitor hepatic function and interrupt, dose reduce, or discontinue SUTENT as recommended. • Hepatotoxicity: Fatal liver failure has been observed. Monitor liver function tests at baseline, during each cycle, and as clinically indicated. Interrupt SUTENT for Grade 3 hepatotoxicity until resolution to Grade ≤1 or baseline and resume SUTENT at a reduced dose, discontinue if no resolution. Discontinue SUTENT in patients with Grade 4 hepatoxicity, in patients who have subsequent severe changes in liver function tests or other signs and symptoms of liver failure. • Cardiovascular Events: Myocardial ischemia, myocardial infarction, heart failure, cardiomyopathy, and decreased left ventricular ejection fraction (LVEF) to below the lower limit of normal including death have occurred.

The following clinically significant adverse reactions are described elsewhere in the labeling. • Hepatotoxicity • Cardiovascular Events • QT Interval Prolongation and Torsade de Pointes • Hypertension • Hemorrhagic Events • Tumor Lysis Syndrome • Thrombotic Microangiopathy • Proteinuria • Dermatologic Toxicities • Reversible Posterior Leukoencephalopathy Syndrome • Thyroid Dysfunction • Hypoglycemia • Osteonecrosis of the Jaw • Impaired Wound Healing • The most common adverse reactions (≥25%) are fatigue/asthenia, diarrhea, mucositis/stomatitis, nausea, decreased appetite/anorexia, vomiting, abdominal pain, hand-foot syndrome, hypertension, bleeding events, dysgeusia/altered taste, dyspepsia, and thrombocytopenia.

• CYP3A4 Inhibitors: Consider dose reduction of SUTENT when administered with strong CYP3A4 inhibitors. • CYP3A4 Inducers: Consider dose increase of SUTENT when administered with strong CYP3A4 inducers.

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).