About AFINITOR^® for Advanced Renal Cell Carcinoma

AFINITOR (everolimus) is the first and only therapy with Phase III evidence after a VEGF^**-targeted therapy

The treatment of advanced renal cell carcinoma has evolved rapidly in the last few years. The emergence of multiple new treatments has led to frequent use of sequential VEGF tyrosine kinase inhibitor (TKI) therapy. Until now, no treatment demonstrated Phase III evidence after disease progression on an initial VEGF-targeted therapy. AFINITOR is the first and only therapy with Phase III evidence after a VEGF-targeted therapy. AFINITOR is a once-daily, oral inhibitor of mTOR (mammalian target of rapamycin) indicated for the treatment of advanced renal cell carcinoma in patients whose disease has progressed on or after treatment with VEGF-targeted therapy.¹

The active ingredient in AFINITOR (everolimus) tablets has been proven in clinical trials to directly inhibit mTOR. Unlike other therapies that primarily inhibit tumor angiogenesis, the direct inhibition of mTOR by AFINITOR has been found to result in:

• Reduced tumor cell growth and proliferation²
• Decreased tumor angiogenesis^2,3
• Inhibited cell metabolism^4,5

In patients with advanced renal cell carcinoma whose disease has progressed on or after VEGF-targeted therapy failure, AFINITOR may be an option.

**VEGF: vascular endothelial growth factor

References:
1. AFINITOR [summary of product information]. Basel, Switzerland: Novartis Pharma AG.
2. Dancy JE. Inhibitors of the mammalian target of rapamycin. Expert Opin Investig Drugs. 2005; 14:313-328.
3. Humar R, Keifer FN, Berns H, Resink TJ, Battegay EJ. Hypoxia enhances vascular cell proliferation and angiogenesis in vitro via rapamycin (mTOR) dependent signaling. FASEB J 2002;16:771-780.
4. Wullschleger S, Loewith R, Hall MN,TOR signaling in growth and metabolism. Cell. 2006;124:471-484.
5. Edinger AL, Thompsonj CB, Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake. Mol Biol Cell. 2002;13:2276-2288.