HAMBURG, GermanyThe steroidal aromatase inactivator
exemestane (Aromasin) is safe and provides superior progression-free survival,
compared with tamoxifen, in the treatment of postmenopausal woman diagnosed
with hormone-responsive metastatic breast cancer, according to the first
head-to-head front-line phase III trial comparing the two agents. Robert
Paridaens, MD, of the University Hospital Gasthuisberg, Leuven, Belgium,
presented the findings at the 4th European Breast Cancer Conference (abstract
The EORTC’s (European Organization for Research and
Treatment of Cancer) Specialized Breast Group initiated the randomized,
open-label, phase II-III trial in 1996. The trial aimed to further document the
safety profile of exemestane and to determine if exemestane-treated patients
had at least a 3-month increase in progression-free survival over tamoxifen.
"This trial was initiated as a phase II study with the possibility of extending
to phase III if results were promising," Dr. Paridaens said.
Patients with measurable disease were enrolled in the trial
if they had not received hormone therapy for metastatic breast cancer and had
either a hormone-receptor-positive cancer or an unknown status with a long
disease-free period. Patients were randomized to exemestane 25 mg daily or
tamoxifen 20 mg daily.
The results of the initial phase II study, which included
122 patients, showed a promising overall response rate, clinical benefits rate,
and response duration favoring exemestane. Furthermore, serious toxicity was
low, and exemestane was generally well tolerated, with no adverse effects on
the lipid profile. As a result, the investigators decided to extend the study
to phase III. Between October 1996 and July 2002, 382 patients from 81
institutions in 25 countries were recruited to participate in the phase III
Data analysis showed a median progression-free survival for
patients taking exemestane of 9.95 months, compared with 5.72 months for those
Response rates were also higher in the exemestane arm: 7.4%
complete response (14 patients) and 36.8% partial response (71 patients) for
exemestane, compared with 2.6% (5 patients) and 26.6% (52 patients),
respectively, for tamoxifen. Dr. Paridaens said that regardless of the site of
the metastasis, the investigators generally saw more responses in patients
taking exemestane than in those taking tamoxifen.
To date, 284 (74%) of the participating patients have
experienced disease progression or have died. The investigators are currently
assessing the trial data further, and the complete overall survival data will
be released later this year.
"The main endpoint of treatment in advanced disease is
control of symptomsin other words, progression-free survival with the fewest
possible adverse effects because maintaining quality of life in incurable
disease is essential," Dr. Paridaens said. He noted that both aromatase
inhibitors and tamoxifen are often associated with hot flushes and menopausal
Further, women taking aromatase inhibitors often complain
about joint and muscular aches. However, the aromatase inhibitors are less
likely than tamoxifen to be associated with thromboembolic events, and, unlike
tamoxifen, they are not associated with an increased risk of endometrial
According to Dr. Paridaens, one interesting finding emerging
from this study is the lack of adverse effects on the patients’ lipid profile
with exemestane. "This contrasts with results seen in studies of nonsteroidal
aromatase inhibitors," he said. "Whether this will translate into greater
long-term cardiovascular safety or whether it is an indication for use of
exemestane in woman with abnormal lipid measurements needs to be demonstrated
in future clinical studies."
Based on the study outcomes, the investigators concluded that exemestane is
a good choice for first-line treatment in hormone-responsive metastatic breast
cancer. Further, Dr. Paridaens said, its safety profile makes it an attractive
option for adjuvant therapy or to prevent breast cancer in high-risk women.