Everolimus (Afinitor)

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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).[1][2][3]
Route: PO
Extravasation: n/a

  • Anecdotally, taking the pill in a small amount of whipped/sour cream[4] or putting the pill in a marshmallow[5] 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 or the prescribing information.[1]

Diseases for which it is established (work in progress)

Diseases for which it is used

Patient drug information

History of changes in FDA indication

HR+ Breast cancer

Neuroendocrine tumor

Pancreatic NET

Renal cell carcinoma

Tuberous sclerosis complex-associated renal angiomyolipoma

  • 2012-04-26: Accelerated approval for adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. (Based on EXIST-2)
    • 2016-02-18: Converted to regular approval

Tuberous sclerosis complex-associated subependymal giant cell astrocytoma

  • 2010-10-29: Accelerated approval for subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS) who require therapeutic intervention but are not candidates for curative surgical resection. (Based on CCHMC 06-07-50)
    • 2016-01-29: Converted to regular approval for subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS) who require therapeutic intervention but are not candidates for curative surgical resection. (Based on EXIST-1)

History of changes in EMA indication

  • 2009-08-02: Initial marketing authorization as Afinitor. Afinitor is intended for the treatment of patients with advanced renal cell carcinoma, whose disease has progressed on or after treatment with VEGF-targeted therapy.
  • 2011-08-24: Extension of indication to include Afinitor is indicated for the treatment of unresectable or metastatic, well- or moderately-differentiated neuroendocrine tumours of pancreatic origin in adults with progressive disease.
  • 2012-06-21: Extension of indication to include Afinitor for the treatment of hormone receptor-positive, HER2/neu negative advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor.
  • 2016-05-26: Extension of indication to include a new indication for the treatment of unresectable or metastatic, well-differentiated non-functional neuroendocrine tumours of gastrointestinal or lung origin in adults with progressive disease.

History of changes in Health Canada indication

  • 2011-06-30: Initial notice of compliance with conditions
  • 2016-09-23: Conditions were met

History of changes in PMDA indication

  • 2007-01-26: Initial approval for the prophylaxis of organ rejection in cardiac transplant.
  • 2010-01-20: New additional indication and a new dosage for the treatment of unresectable or metastatic renal cell carcinoma.
  • 2011-12-22: New additional indication and a new dosage for the treatment of pancreatic neuroendocrine tumor.
  • 2012-11-21: New additional indications and a new dosage for the treatment of renal angiomyolipoma associated with tuberous sclerosis complex and subependymal giant cell astrocytoma associated with tuberous sclerosis complex.
  • 2014-03-17: New additional indication and a new dosage for the treatment of unresectable or recurrent breast cancer.
  • 2016-08-26: revised indication from "pancreatic neuroendocrine tumor" to "neuroendocrine tumor."

Also known as

  • Code names: RAD-001
  • Brand names: Afilimus, Advacan, Afinitor, Afinitor Disperz, Certican, Everbliss, Evercon, EverGraf, Evermil, Everomus, Everotaj, Evertor, Lanolimus, Natlimus, Rapact, Rolimus, Torinat, Votubia, Xevirol, Zortress

References