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Comparison of Fulvestrant Versus Tamoxifen for the Treatment of Advanced Breast Cancer in Postmenopausal Women Previously Untreated With Endocrine Therapy: A Multinational, Double-Blind, Randomized Trial

From the Christie Hospital and Holt Radium Institute, Manchester; City Hospital, Nottingham; Belvoir Park Hospital, Belfast, United Kingdom; Cancer Research Centre of Russian Academy of Medical Sciences, Moscow, Russia; Breast Center at Baylor College of Medicine and the Methodist Hospital, Houston, TX; Istituto Nazionale Tumori, Milan, Italy; National Cancer Center Hospital, Tokyo, Japan; and AstraZeneca, Wilmington, DE

Address reprint requests to Anthony Howell, MD, Christie Hospital National Health Service Trust, Wilmslow Rd, Manchester M20 9BX, UK; e-mail: maria.parker{at}christie-tr.nwest.nhs.uk

PURPOSE: To evaluate the efficacy and tolerability of fulvestrant (Faslodex; AstraZeneca Pharmaceuticals LP, Wilmington, DE), a new estrogen receptor (ER) antagonist that downregulates ER and has no agonist effects, versus tamoxifen, an antiestrogen with agonist and antagonist effects, for the treatment of advanced breast cancer in postmenopausal women.

PATIENTS AND METHODS: In this multicenter, double-blind, randomized trial, patients with metastatic/locally advanced breast cancer previously untreated for advanced disease were randomly assigned to receive either fulvestrant (250 mg, via intramuscular injection, once monthly; n = 313) or tamoxifen (20 mg, orally, once daily; n = 274). Patients' tumors were positive for ER (ER+) and/or progesterone receptor (PgR+), or had an unknown receptor status.

RESULTS: At a median follow-up of 14.5 months, there was no significant difference between fulvestrant and tamoxifen for the primary end point of time to progression (TTP; median TTP, 6.8 months and 8.3 months, respectively; hazard ratio, 1.18; 95% CI, 0.98 to 1.44; P = .088). In a prospectively planned subset analysis of patients with known ER+ and/or PgR+ tumors (78%), median TTP was 8.2 months for fulvestrant and 8.3 months for tamoxifen (hazard ratio, 1.10; 95% CI, 0.89 to 1.36; P = .39). The objective response rate for the overall population was 31.6% with fulvestrant and 33.9% with tamoxifen, and 33.2% and 31.1%, respectively, in the known hormone receptor–positive subgroup. Both treatments were well tolerated.

CONCLUSION: In the overall population, between-group differences in efficacy end points favored tamoxifen, and statistical noninferiority of fulvestrant could not be demonstrated. However, in patients with hormone receptor–positive tumors, fulvestrant had similar efficacy to tamoxifen and was well tolerated.

Supported by AstraZeneca Pharmaceuticals, Wilmington, DE.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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