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