Everolimus Plus Exemestane - A Possible First-Line Therapy for Metastatic Disease

Breast Cancer News
April 24, 2014
Nicole Katze, MA, Editor and Manager, Content Development

Everolimus (Afinitor) and exemestane (Aromasin) taken at the same time may be an effective first-line treatment for hormone receptor-positive breast cancer that metastasized, or spread beyond the breast to other organs, after treatment with another aromatase inhibitor. This finding comes from a new analysis of data from the BOLERO-2 trial.

In this re-analysis of original study data, researchers explored the benefit of giving everolimus plus exemestane versus exemestane alone to women who received only hormonal therapy with an aromatase inhibitor to treat early-stage disease.

Background and Goals

First-line treatments for metastatic breast cancer are the first systemic therapies given to treat the disease. Systemic therapies treat the whole body, and include hormonal and biologic therapies, as well as chemotherapy.

Aromatase inhibitors, or AIs, are hormonal therapies that are FDA approved to treat women who are postmenopausal, or no longer have their monthly period. AIs stop estrogen from being made in a woman’s body by blocking the enzyme aromatase, which helps make it.

The BOLERO-2 trial showed that taking everolimus, an mTOR inhibitor, and exemestane, an AI, at the same time daily nearly doubled breast cancer progression-free survival (PFS) compared with exemestane alone. Progression-free survival is the time from the start of the anticancer treatment until the disease worsens or travels to a distant part of the body.

The everolimus–exemestane pair was approved by the US Food and Drug Administration (FDA) in 2012 to treat women with hormone receptor-positive, HER2-negative metastatic breast cancer (MBC) that got worse after treatment with AIs alone. You can read more about BOLERO-2 and FDA approval of the combination here.

Though BOLERO-2 did not require the pair of medicines to be the first treatment participants received for MBC, a small group of women in this trial had not yet been treated for advanced breast cancer at the start of the trial. These women were treated with aromatase inhibitors for early-stage breast cancer that later progressed to MBC. The AIs were given either before surgery, after surgery, or both.

The BOLERO-2 trial team wanted to find out if everolimus with exemestane was as effective in this group as it was in the overall trial group, and if it was safe to use before other treatments for advanced breast cancer are given.


For this analysis, trial researchers measured PFS and health-related quality of life, how satisfied a person is with life in relation to cancer and its treatment. They did so among 137 women whose first treatment for MBC was everolimus and exemestane taken together.

Read about the design of BOLERO-2 here.

Read more about the overall impact on health-related quality of life here.


Overall, the analysis showed that

  • everolimus plus exemestane, given as a first-line therapy, nearly tripled PFS compared with exemestane alone in women who had disease progression during or after treatment with AIs for early-stage breast cancer
  • those treated with the two medicines at the same time each day as a first-line therapy had the same health-related quality of life as other participant groups
  • the side effects of first-line treatment were the same as those seen in the larger study population

What This Means for You

If you have hormone receptor-positive, metastatic breast cancer, taking the everolimus and exemestane combination may be a suitable first-line treatment option for you. Your doctor will guide you to the best therapies for you.

Though the findings of this study may not change clinical practice right now, they may prompt further research that could one day result in the medicines’ wider use as first-line therapy.

Such research is already under way in the phase II clinical trial BOLERO-4, exploring everolimus plus letrozole as first-line therapy for hormone receptor-positive, HER2-negative metastatic breast cancer. As research continues, doctors may learn more about the benefits of giving everolimus with aromatase inhibitors at once as the first treatment after breast cancer metastasizes.

Beck, T, Hortobagyi, G, Campone, M, Lebrun, F, Deleu, I, et al.  Everolimus plus exemestane as first-line therapy in HR+, HER2- advanced breast cancer in BOLERO-2Breast Cancer Research and Treatment; (2014) 143(3): 459-467.

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Additional Related Topics 
Hormone Receptor-Positive
Hormonal Therapy