Effectiveness and tolerability of fulvestrant in postmenopausal women with hormone receptor-positive breast cancer.

Abstract Fulvestrant, an estrogen receptor antagonist that downregulates the estrogen receptor but has no known agonist effects, has been evaluated in 2 randomized trials involving postmenopausal women with hormone receptor—positive, progressive advanced-stage breast cancer after disease progression with antiestrogen therapy. These phase III studies, from which data were reported separately and in a planned combined analysis, showed that fulvestrant 250 mg per month intramuscularly was at least as effective as anastrozole 1 mg per day orally with respect to the primary endpoint of time to progression as well as secondary efficacy endpoints, which included objective response, clinical benefit, and survival. Both trials showed that patients treated with fulvestrant had a significantly longer duration of response, and a retrospective analysis found that pretreatment with fulvestrant did not preclude response to third-line hormonal therapy. More recently, fulvestrant was shown to be active as first-line hormonal therapy for advanced-stage breast cancer, with overall efficacy similar to that of tamoxifen in patients with hormone receptor—positive disease. Fulvestrant has been well tolerated in comparative trials published to date, translating into low study withdrawal rates and maintenance of quality of life. The incidence of adverse events was similar between the treatment arms in both trials of fulvestrant versus anastrozole, but it was notably lower for fulvestrant relative to tamoxifen in the first-line setting. In light of the results of comparative phase III trials, fulvestrant is effective and well tolerated in the treatment of postmenopausal women with hormone receptor—positive advanced-stage breast cancer.