Adjuvant Treatment in Early Breast Cancer
The Intergroup Exemestane Study 031 (IES) was a randomized, double-blind, multicenter,
multinational study comparing exemestane (25 mg/day) versus tamoxifen (20 or 30
mg/day) in postmenopausal women with early breast cancer. Patients who remained
disease-free after receiving adjuvant tamoxifen therapy for 2 to 3 years were randomized
to receive 3 to 2 years of AROMASIN or tamoxifen to complete a total of 5 years
of hormonal therapy.
The primary objective of the study was to determine whether, in terms of disease-free
survival, it was more effective to switch to AROMASIN rather than continuing tamoxifen
therapy for the remainder of five years. Disease-free survival was defined as the
time from randomization to time of local or distant recurrence of breast cancer,
contralateral invasive breast cancer, or death from any cause.
The secondary objectives were to compare the two regimens in terms of overall survival
and long-term tolerability. Time to contralateral invasive breast cancer and distant
recurrence-free survival were also evaluated
A total of 4724 patients in the intent-to-treat (ITT) analysis were randomized to
AROMASIN (exemestane tablets) 25 mg once daily (N = 2352) or to continue to receive
tamoxifen once daily at the same dose received before randomization (N = 2372).
Demographics and baseline tumor characteristics are presented in Table 1. Prior
breast cancer therapy is summarized in Table 2.
Table 1. Demographic and Baseline Tumor Characteristics from the IES Study of Postmenopausal
Women with Early Breast Cancer (ITT Population)
Table 2. Prior Breast Cancer Therapy of Patients in the IES Study of Postmenopausal
Women with Early Breast Cancer (ITT Population)
After a median duration of therapy of 27 months and with a median follow-up of 34.5
months, 520 events were reported, 213 in the AROMASIN group and 307 in the tamoxifen
group (Table 3).
Table 3. Primary Endpoint Events (ITT Population)
Disease-free survival in the intent-to-treat population was statistically significantly
improved [Hazard Ratio (HR) = 0.69, 95% CI: 0.58, 0.82, P = 0.00003, Table 4, Figure
1] in the AROMASIN arm compared to the tamoxifen arm. In the hormone receptor-positive
subpopulation representing about 85% of the trial patients, disease-free survival
was also statistically significantly improved (HR = 0.65, 95% CI: 0.53, 0.79, P
= 0.00001) in the AROMASIN arm compared to the tamoxifen arm. Consistent results
were observed in the subgroups of patients with node negative or positive disease,
and patients who had or had not received prior chemotherapy. Overall survival was
not significantly different in the two groups, with 116 deaths occurring in the
AROMASIN group and 137 in the tamoxifen group.
Table 4. Efficacy Results from the IES Study of Postmenopausal Women with Early Breast
Cancer
Figure 1. Disease Free Survival in the IES Study of Postmenopausal Women with Early
Breast Cancer (ITT Population)
Treatment of Advanced Breast Cancer
Exemestane 25 mg administered once daily was evaluated in a randomized double-blind,
multicenter, multinational comparative study and in two multicenter single-arm studies
of postmenopausal women with advanced breast cancer who had disease progression
after treatment with tamoxifen for metastatic disease or as adjuvant therapy. Some
patients also have received prior cytotoxic therapy, either as adjuvant treatment
or for metastatic disease.
The primary purpose of the three studies was evaluation of objective response rate
(complete response [CR] and partial response [PR]). Time to tumor progression and
overall survival were also assessed in the comparative trial. Response rates were
assessed based on World Health Organization (WHO) criteria, and in the comparative
study, were submitted to an external review committee that was blinded to patient
treatment. In the comparative study, 769 patients were randomized to receive AROMASIN
(exemestane tablets) 25 mg once daily (N = 366) or megestrol acetate 40 mg four
times daily (N = 403). Demographics and baseline characteristics are presented in
Table 5.
Table 5. Demographics and Baseline Characteristics from the Comparative Study of
Postmenopausal Women with Advanced Breast Cancer Whose Disease Had Progressed after
Tamoxifen Therapy
The efficacy results from the comparative study are shown in Table 6. The objective
response rates observed in the two treatment arms showed that AROMASIN was not different
from megestrol acetate. Response rates for AROMASIN from the two single-arm trials
were 23.4% and 28.1%.
Table 6. Efficacy Results from the Comparative Study of Postmenopausal Women with
Advanced Breast Cancer Whose Disease Had Progressed after Tamoxifen Therapy
There were too few deaths occurring across treatment groups to draw conclusions
on overall survival differences. The Kaplan-Meier curve for time to tumor progression
in the comparative study is shown in Figure 2.
Figure 2. Time to Tumor Progression in the Comparative Study of Postmenopausal Women
with Advanced Breast Cancer Whose Disease Had Progressed After Tamoxifen Therapy
