Initial data from a phase II study of exemestane (Aromasin) as
first-line treatment of advanced breast cancer in postmenopausal
women suggest that the new agent may extend the time that patients
remain free of tumor growth compared to tamoxifen (Nolvadex).
Tamoxifen is currently the hormonal agent of choice for first-line
treatment of advanced breast cancer. The results of this study were
presented at the annual meeting of the American Society of Clinical
New Standards of Care
The study compared the activity and safety of exemestane (25 mg/d)
with tamoxifen (20 mg/d) as first-line hormonal therapy in
postmenopausal women with advanced breast cancer. From 97 randomized
patients, data on response are available for 63 and on toxicity, for
76. In the study, the median time to tumor progression in patients
treated with exemestane was 8.9 months, compared with 5.2 months for
those treated with tamoxifen.
These preliminary results are striking, said Robert J.
Paridaens, MD, PhD, professor and head of the medical oncology
clinic, University Hospital Gasthuisberg, Catholic University Leuven,
Leuven, Belgium. The data suggest that Aromasin challenges the
standard of care, which may be confirmed by moving to a phase III
trial involving a larger number of patients in order to allow a true
and statistically valid comparison.
The Trials Continue
Approved by the US Food and Drug Administration in the fourth quarter
of 1999, exemestane is indicated for the treatment of advanced breast
cancer in postmenopausal women whose tumors have stopped responding
to antiestrogen therapy, such as tamoxifen. It is the first in a new
class of oral hormonal inactivator therapies that work by selectively
targeting and irreversibly binding to the aromatase enzyme, which is
required to produce estrogen. Exemestane interferes with the supply
of estrogen to cancerous cells and prevents the cells from continuing
The unique mechanism of action and other clinical trial results to
date prompted the European Organization for Research and Treatment of
Cancer (EORTC) to conduct this phase II study. Based on these initial
results, the EORTC initiated an identically designed large phase III
trial. A National Surgical Adjuvant Breast and Bowel Project (NSABP)
study of exemestane began in mid-2000.
Exemestane is also being studied for chemoprevention and was found to
be well tolerated. Women treated with exemestane experienced the
following side effects, compared to those treated with tamoxifen:
grade 2/3 fatigue (5% vs 13%), pain (11% vs 18%), hot flushes (3% vs
15%), sweating (0% vs 10%), edema (3% vs 8%), nausea (3% vs 8%), and
dyspnea (11% vs 5%). There was no difference between the two groups
in the incidence of weight gain (5% vs 5%).