Longer Response With Use of Fulvestrant Than Anastrozole in Advanced Breast Cancer

ORLANDO—Compared with the aromatase inhibitor anastrozole (Arimi-dex), mean duration of response is significantly greater with fulvestrant (Faslo-dex) in postmenopausal women with advanced breast cancer who have progressed on prior endocrine therapy. For other key endpoints, fulvestrant was at least as effective as anastrozole, according to a poster presentation at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 160).

Fulvestrant is an estrogen-receptor downregulator with no known agonist activity, said Leroy M. Parker, MD, associate clinical professor of medicine, Harvard Medical School, Dana-Farber Cancer Institute.

He reported on combined results from two randomized phase III multicenter trials enrolling 851 patients: an open-label trial from centers in Europe, South Africa, Australia enrolling 451 patients and a double-blind North America trial enrolling 400 patients. In each trial, patients received either monthly intramuscular injections of 250 mg fulvestrant or once-daily oral 1 mg anastrozole.

Included women were postmenopausal and hormone sensitive, and had received no more than one prior endocrine treatment (including prior fulvestrant or aromatase inhibitors). They had objective evidence of recurrence of disease progression. Mean age was 63.4 years in both groups.

Previously presented findings at follow-up of 15.1 months had shown median time to progression, the primary endpoint, to be 5.5 months for fulvestrant and 4.1 months for anastrozole, with objective response rates of 19.2% and 16.5%, respectively. Dr. Parker presented updated results with a median of 22.1 months of follow-up.

[Separate reports on both studies with median follow-up of 16.8 months for the US trial and 14.4 months for the European trial were recently published in the August 15, 2002, issue of the Journal of Clinical Oncology.]

Efficacy Results

The updated combined results with a median follow-up of 22.1 months showed time to progression of 5.4 months for fulvestrant (n = 428) and 4.1 months for anastrozole (n = 423). Overall response rates (complete plus partial responses) were 19.6% and 17.3%, respectively, and clinical benefit rates, defined as complete response plus partial response plus stable disease for at least 24 weeks, were 43.7% and 41.1%, respectively. Differences were not statistically significant.

In responding patients, median duration of response was 16.7 months for ful-vestrant and 13.6 months for anastrozole. A new statistical analysis of duration of response was performed for all randomized patients using as a duration of response definition for responders, time from onset of response to time of progression, and for nonresponders, zero. Mean duration of response in this analysis was 30% greater for fulvestrant than for anastrozole. The ratio of average response durations was 1.30 (P = .0003).

Both agents were well tolerated with a similar incidence of adverse events, with the exception of joint disorders, which occurred significantly less often with fulvestrant (5.4% vs 10.6% for anas-trozole, P = .0036).

Dr. Parker concluded that fulvestrant is at least as effective as anastrozole with respect to time to progression, overall response rate, and clinical benefit in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy. Fulvestrant is associated with a significantly greater mean duration of response than anastrozole and, he said, "will be a valuable additional treatment option" in this setting.

"Faslodex is clearly a new drug in our armamentarium," said poster discussant Paul Edward Gross, MD, Princess Mar-garet Hospital, University of Toronto, Canada. He commented further, "The question that is perplexing all of us—and we don’t have the data yet—is, What is the optimal next treatment after you have treated a patient with tamoxifen [Nolvadex]? Aromatase inhibitors clearly have the data in that setting, but so too now does Faslodex. . . . We have to wait for the clinical trials."