Clinical Trial Resource Center

Clinical Trial Resource Center

FDA Approved Drugs » 2012
Medical Areas: Obstetrics/Gynecology (Women’s Health) | Oncology | Family Medicine

View By:Year | Company | Conditions | Therapeutic Areas | Drug Names

Afinitor (everolimus)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company: Novartis
Approval Status: Approved July 2012
Treatment Area: hormone receptor-positive, HER2-negative breast cancer

General Information

Afinitor (everolimus), an inhibitor of mTOR (mammalian target of rapamycin), is an antineoplastic agent.

Afinitor is specifically approved for the treatment of 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.

Afinitor is supplied as a tablet for oral administration. The recommended dose of Afinitor for breast cancer is 10 mg, to be taken once daily, at the same time every day, either consistently with food or consistently without food.

Clinical Results

FDA Approval
The FDA approval of Afinitor for the treatment of advanced hormone receptor-positive, HER2-negative breast cancer was based on a randomized, double-blind, multicenter study in 724 postmenopausal women with estrogen receptor-positive, HER 2/neu-negative advanced breast cancer with recurrence or progression following prior therapy with letrozole or anastrozole. The subjects were randomized to Afinitor 10 mg/day plus exemestane 25 mg/day (n = 485) or to placebo plus exemestane 25 mg/day (n = 239). The primary endpoint was progression-free survival (PFS) evaluated by RECIST (Response Evaluation Criteria in Solid Tumors), based on investigator (local radiology) assessment. The median progression-free survival at the time of the final PFS analysis was 7.8 and 3.2 months in the Afinitor and placebo arms, respectively [p < 0.0001]. Objective response rate was 12.6% in the Afinitor plus exemestane arm vs. 1.7% in the placebo plus exemestane arm. There were 3 complete responses (0.6%) and 58 partial responses (12.0%) in the Afinitor plus exemestane arm. There were no complete responses and 4 partial responses (1.7%) in the placebo plus exemestane arm.

Side Effects

Adverse events associated with the use of Afinitor for the treatment of advanced hormone receptor-positive, HER2-negative breast cancer may include, but are not limited to, the following:

  • stomatitis
  • infections
  • rash
  • fatigue
  • diarrhea
  • edema
  • abdominal pain
  • nausea
  • fever
  • asthenia
  • cough
  • headache
  • decreased appetite

Mechanism of Action

Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), 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 with mTOR complex 1 (mTORC1) and thus inhibition of mTOR kinase activity.

Literature References

Beaver JA, Park BH The BOLERO-2 trial: the addition of everolimus to exemestane in the treatment of postmenopausal hormone receptor-positive advanced breast cancer. Future Oncology 2012 Jun;8(6):651-7

Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. New England Journal of Medicine 2012 Feb 9;366(6):520-9.

Additional Information

For additional information regarding Afinitor for advanced hormone receptor-positive, HER2-negative breast cancer, please visit the Afinitor web page.