Afinitor (everolimus)

Company
Novartis

Approval Status
Approved March 2009

Treatment for
renal cell carcinoma

Possible similar drugs
Afinitor; Afinitor; Afinitor

Areas
Urology & Kidneys , Cancer & Oncology

Afinitor is an inhibitor of mTOR (mammalian target of rapamycin), a serine-threonine kinase, downstream of the PI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers. Everolimus binds to an intracellular protein, FKBP-12, resulting in an inhibitory complex formation and inhibition of mTOR kinase activity. Inhibition of mTOR by everolimus has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or in vivo studies.

Afinitor is specifically indicated for the treatment of advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib.

Afinitor is supplied as a 5 mg or 10 mg tablet designed for oral administration. The recommended initial dose of the drug is 10 mg, to be taken once daily at the same time every day, either with or without food. Afinitor tablets should be swallowed whole with a glass of water; they should not be chewed or crushed.

FDA Approval
FDA approval of Afinitor was based on the results of a clinical trial. This international, multicenter, randomized, double-blind study enrolled 416 subjects with metastatic renal cell carcinoma whose disease had progressed despite prior treatment with sunitinib, sorafenib, or both sequentially. The subjects received Afinitor 10 mg once daily or placebo, both in conjunction with best cupportive care. After documented radiological progression, subjects could be unblinded by the investigator: those randomized to placebo were then able to receive open-label Afinitor 10 mg daily. The primary endpoint was progression-free survival (PFS), documented using RECIST criteria. The median progression-free survival was 4.9 months for Afinitor versus 1.9 months for placebo (p<0.0001).

Ongoing Study Commitments

  • Novartis has agreed to conduct a trial in patients with severe hepatic impairment (Child Pugh Class C). This trial need not be conducted in patients with cancer and a single dose evaluation will be appropriate.
    Final Protocol Submission: May 14, 2009
    Trial Start Date: October 14, 2009
    Final Report Submission: April 14, 2011
  • Novartis has agreed to submit the final, per-protocol overall survival analysis of protocol C2240 which was to be conducted 2 years after randomization of the last patient.
    Protocol Submission: July 27, 2006
    Trial Start Date: December 6, 2006
    Final Report Submission: June 2010

Adverse events associated with the use of Afinitor may include, but are not limited to, the following:

  • Stomatitis
  • Infections and infestations
  • Asthenia
  • Fatigue
  • Diarrhea
  • Cough
  • Rash
  • Nausea
  • Anorexia

Afinitor is an inhibitor of mTOR (mammalian target of rapamycin), a serine-threonine kinase, downstream of the PI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers. Everolimus binds to an intracellular protein, FKBP-12, resulting in an inhibitory complex formation and inhibition of mTOR kinase activity. Everolimus reduced the activity of S6 ribosomal protein kinase (S6K1) and eukaryotic elongation factor 4E-binding protein (4E-BP), downstream effectors of mTOR, involved in protein synthesis. In addition, everolimus inhibited the expression of hypoxia-inducible factor (e.g., HIF-1) and reduced the expression of vascular endothelial growth factor (VEGF). Inhibition of mTOR by everolimus has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or in vivo studies.

For additional information regarding Afinitor or renal cell carcinoma, please visit the Afinitor web page.

Afinitor_1018 Drug Information

The Afinitor_1018 drug information shown above is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.

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