Originally published as JCO Early Release 10.1200/JCO.2002.10.058 on July 1 2002

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Double-Blind, Randomized Trial Comparing the Efficacy and Tolerability of Fulvestrant Versus Anastrozole in Postmenopausal Women With Advanced Breast Cancer Progressing on Prior Endocrine Therapy: Results of a North American Trial

From the Breast Center at Baylor College of Medicine, Methodist Hospital, US Oncology, and M.D. Anderson Cancer Center, Houston, and Baylor-Sammons Cancer Center, Dallas, TX; Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center, Boston, MA; Lombardi Cancer Center, Washington, DC; Ottawa Regional Cancer Center, Ottawa, Ontario, Canada; Hematology Oncology Association VA Ltd, Richmond, VA; Louisiana State University Health Science Center, Shreveport, LA; and AstraZeneca, Macclesfield, United Kingdom.

Address reprint requests to C.K. Osborne, MD, Breast Center, Baylor College of Medicine, 1 Baylor Plaza, MS 600, Houston, TX 77030; email: kosborne{at}breastcenter.tmc.edu

PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) with anastrozole in the treatment of advanced breast cancer in patients whose disease progresses on prior endocrine treatment.

PATIENTS AND METHODS: In this double-blind, double-dummy, parallel-group study, postmenopausal patients were randomized to receive either an intramuscular injection of fulvestrant 250 mg once monthly or a daily oral dose of anastrozole 1 mg. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rate, duration of response (DOR), and tolerability.

RESULTS: Patients (n = 400) were followed for a median period of 16.8 months. Fulvestrant was as effective as anastrozole in terms of TTP (hazard ratio, 0.92; 95.14% confidence interval [CI], 0.74 to 1.14; P = .43); median TTP was 5.4 months with fulvestrant and 3.4 months with anastrozole. OR rates were 17.5% with both treatments. Clinical benefit rates (complete response + partial response + stable disease 24 weeks) were 42.2% for fulvestrant and 36.1% for anastrozole (95% CI, -4.00% to 16.41%; P = .26). In responding patients, median DOR (from randomization to progression) was 19.0 months for fulvestrant and 10.8 months for anastrozole. Using all patients, DOR was significantly greater for fulvestrant compared with anastrozole; the ratio of average response durations was 1.35 (95% CI, 1.10 to 1.67; P < 0.01). Both treatments were well tolerated.

CONCLUSION: Fulvestrant was at least as effective as anastrozole, with efficacy end points slightly favoring fulvestrant. Fulvestrant represents an additional treatment option for postmenopausal women with advanced breast cancer whose disease progresses on tamoxifen therapy.

This article was published ahead of print at www.jco.org.

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