This phase II, multicentre, open-label, clinical trial evaluated antitumoral efficacy, tolerability and endocrine effects following 25 mg of treatment with oral
exemestane given daily to postmenopausal women with metastatic
breast cancer. Eligibility criteria included oestrogen and/or
progesterone positivity or a prior response to hormonal
therapy if receptor status was unknown; prior failure to
tamoxifen therapy; and progressive disease. Patients were divided into three strata: patients who did not respond to
tamoxifen or progressed after disease stabilisation (SD) for less than 6 months (stratum 1); patients who, after an initial response or SD lasting at least 6 months, experienced
disease progression whilst on
tamoxifen (stratum 2); patients with recurrent metastatic disease during or within 12 months of discontinuing adjuvant
tamoxifen (stratum 3). Of the 137 patients who received
exemestane, 4 experienced a complete response (CR) and 28 a partial response (PR), for an overall response rate of 23%. Another 33 patients had SD for > or = 24 weeks, resulting in an overall success rate of 47%. The median time to objective response was 16.1 weeks (95% confidence interval (CI) 9.9-24.1). The median response duration was 69.4 weeks, the median duration of overall success 59.1 weeks, the median time to progression (
TTP) 25.1 weeks and the median
time to treatment failure (TTF) 24 weeks. Response to previous hormonal
therapy had little effect on the results, except that there was a trend toward a higher overall success rate in patients who did not respond to previous hormonal
therapy. After 8 weeks of
therapy, serum levels of
oestradiol (E2), oestrone (E1) and
oestrone sulphate (E1S) were suppressed to 15.2%, 9.7% and 10.7% of baseline, respectively. The most common adverse events of
drug-related or indeterminate cause were hot flushes (14%),
dizziness (9%),
nausea (8%) and increased sweating (5%).
Exemestane had a favourable effect on performance status and tumour-related signs and symptoms, both of which improved or stabilised in approximately 67% and 68% of patients respectively.
Exemestane is a unique
therapy that is highly active and well tolerated as a new treatment for women with metastatic
breast cancer.