On July 20, 2012, the U.S. Food and Drug Administration (FDA) gave us another option for treating postmenopausal patients with metastatic, ER-positive, HER2-negative breast cancer whose disease has progressed on Arimidex or Femara by approving Afinitor (everolimus) in combination with Aromasin (exemestane). This new approval was based on the BOLERO-2 trial which was a randomized, double-blind, multicenter trial conducted in 724 postmenopausal women.  Patients were randomized to receive either Afinitor 10 mg/day plus Aromasin 25 mg/day or to placebo plus Aromasin 25 mg/day. Both Aromasin and Afinitor are oral drugs.

Aromasin is an aromatase inhibitor which works by lowering estrogen levels in postmenopausal women. This trial was based on the observation that resistance (either not responding or stopping responding) to hormonal therapy is associated with a tumor being able to use pathways other than the estrogen pathway to survive and grow. One example of this is activation of the mammalian target of rapamycin (mTOR) signaling pathway in cells. Afinitor targets the mTOR pathway and is classified as an mTOR inhibitor. 

On the BOLERO-2 trial, the median progression-free survival (PFS) was longer for the patients receiving Afinitor (7.8 vs 3.2 months). These results were consistent regardless of age, race, presence or extent of visceral metastases (such as liver metastases), and response to prior hormonal therapy.  The response rate was also better for the patients receiving Afinitor (12.6% vs 1.7%).  The analysis of overall survival (OS) was not significant however this was an interim analysis.  The final OS analysis isn’t expected to become available until June, 2014.

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