Everolimus (Afinitor)

General information

Class/mechanism: mTOR kinase inhibitor; mTOR (mammalian target of rapamycin) is a serine-threonine kinase downstream of the PI3K/AKT pathway. In vitro, everolimus has been found to reduce cell proliferation, angiogenesis, and glucose uptake. Everolimus forms inhibitory complexes with mTORC1 by binding to the intracellular protein FKBP-12. Reduces activity of downstream effectors of mTOR that are involved in protein synthesis, S6 ribosomal protein kinase (S6K1) and eukaryotic elongation factor 4E binding protein (4E-BP1). Reduces expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF-1).
Route: PO
Extravasation: n/a

• Anecdotally, taking the pill in a small amount of whipped/sour cream or putting the pill in a marshmallow may decrease the likelihood of developing stomatitis/mucositis.

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is used

• B-cell acute lymphoblastic leukemia
• Breast cancer
• Diffuse large B-cell lymphoma
• Hodgkin lymphoma
• Mantle cell lymphoma
• Neuroendocrine tumor
• Pancreatic NET
• Peripheral T-cell lymphoma
• Renal cell carcinoma
• Thymoma
• Waldenström macroglobulinemia

Patient drug information

• Everolimus (Afinitor) package insert PDF pages 40-46
• Everolimus (Afinitor) patient drug information (Chemocare)
• Everolimus (Afinitor) patient drug information (UpToDate)

History of changes in FDA indication

• 3/30/2009: Initial FDA approval for the treatment of patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib.
• 10/29/2010: Approval expanded to include subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS) who require therapeutic intervention but are not candidates for curative surgical resection.
• 5/5/2011: Approval expanded to include progressive neuroendocrine tumors of pancreatic origin (PNET) that is unresectable, locally advanced or metastatic.
• 4/26/2012: Approval expanded to include adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery.
• 7/20/2012: Approval expanded to include postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole or anastrozole.
• 2/26/2016: Approval expanded for the treatment of adult patients with progressive, well-differentiated non-functional, neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin with unresectable, locally advanced or metastatic disease.

Also known as

• Code names: RAD001, RAD-001
• Brand names: Advacan, Afinitor, Afinitor Disperz, Certican, Everecan, EverGraf, Evermil, Evertor, Rapact, Rolimus, Votubia, Zortress