Everolimus in Combination With Exemestane can Improve Disease-free Survival in Advanced Breast Cancer

Advanced breast cancer is treated with surgery, radiotherapy and chemotherapy. Some breast cancers grow in the presence of the female hormones estrogen and progesterone.  Thus, blocking the effects of these hormones using medications helps in controlling the growth of the cancer and preventing recurrences.

Drugs used in the treatment of breast cancer that block the effect of hormones include letrozole, anastrozole and exemestane.  These drugs are aromatase inhibitors, that is, they block the production of estrogen in post-menopausal women.  Other drugs like estrogen receptor antagonists fulvestrant and tamoxifen block the effect of estrogen in the breast tissues.

Unfortunately, there are still some cancers that do not respond to these drugs as well.  Studies indicate that there is yet another drug called everolimus, which is useful in these cases.  It is currently indicated in advanced cancers, which include those affecting the pancreas and the kidney.  Some formulations are approved in the prevention of kidney transplant rejection.

In a clinical trial conducted by Novartis, the manufacturer of the drug everolimus under the trade name Afinitor, the use of everolimus was tested in advanced breast cancer patients not responding to other hormonal treatments.  The patients included in the study had hormone-responsive advanced breast cancer but did not respond to drugs like letrozole or anastrozole or had a recurrence within 1 year of therapy.  The patients were administered 10mg of everolimus orally or placebo in addition to exemestane 25 mg daily.  They were treated till they either showed disease progression, unacceptable toxicity, or if the patients withdrew consent.  Dose could be reduced in case of side effects.

A total of 724 women from 24 countries were included in the study.  Among these, 485 patients received the combination of everolimus and exemestane and 239 patients required exemestane with placebo in the period between June 2009 and January 2011.  By February 2011, 227 patients in the combination-therapy group and 69 in the exemestane-alone group continued to receive treatment.  The most common reason for discontinuation of treatment was progression of disease, which was almost double in the exemestane-alone group.

In terms of efficacy of the drug combination, the duration of progression-free survival was much more in the combination-therapy group as compared with the placebo plus exemestane group (6.9 months versus 2.8 months).  The efficacy was based on the results of imaging studies assessed by local investigators.

On the other hand, the number of adverse effects was almost double in the combination-therapy group.  Seven deaths in the combination group were attributable to treatment-related adverse effects.  These included 2 deaths from sepsis, one each from pneumonia, bleeding from the tumor, stroke, kidney failure, and suicide.  Other common adverse effects included stomatitis (inflammation of the lining of the mouth), anemia, difficulty with breathing, fatigue and pneumonitis or inflammation of the lung.

Thus, though a benefit was observed with the treatment comprising of everolimus plus exemestane, the benefits should be weighed against the risks of side effects.  Since very few options are available in this drug-resistant advanced breast cancer group, the combination of everolimus plus exemestane may be worth exploring.

Reference:

Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast Cancer; José Baselga, et al; NEJM; December 7, 2011

Source-Medindia