Phase II Study Suggests Survival Benefit With First-Line Fulvestrant vs Anastrozole in Advanced Breast Cancer


Key Points

  • Overall survival analysis was added after time to progression results were available.
  • Fulvestrant appeared to have a survival benefit vs anastrozole.
  • A phase III trial is under way to compare fulvestrant with anastrozole in hormonal therapy-naive patients with advanced breast cancer.

Overall survival data from a phase II study, reported in the Journal of Clinical Oncology by Ellis et al, suggest a benefit of first-line fulvestrant (Faslodex) vs anastrozole in postmenopausal women with estrogen receptor–positive advanced breast cancer. The study protocol was amended to include overall survival analysis only after time to progression results had been analyzed.

Study Details

In the open-label study, 205 patients from nine countries were randomly assigned to receive fulvestrant 500 mg on days 0, 14, and 28 and every 28 days thereafter or anastrozole 1 mg daily. The primary endpoint (clinical benefit rate of 72.5% and 67.0%) and a follow-up analysis (median time to progression = 23.4 months and 13.1 months) have already been reported. The protocol was amended to assess overall survival (by unadjusted log-rank test) after approximately 65% of patients had died.

Among the 205 patients, 35 (16 in the fulvestrant group and 19 in the anastrozole group) did not participate in the overall survival follow-up phase, with their data being censored at the date they were last known to be alive; data until this time were included in the analysis. For 20 of these patients, centers they attended declined to contribute to the overall survival follow-up. In total, 72% of the fulvestrant group and 78% of the anastrozole group had not received endocrine treatment for early disease; those who received such treatment almost exclusively received tamoxifen.

Survival Analysis

At data cutoff, 61.8% of the fulvestrant group and 71.8% in the anastrozole group were known to have died. Median overall survival was 54.1 months in the fulvestrant group vs 48.4 months in the anastrozole group (hazard ratio = 0.70, P = .04). Totals of 64% and 58% were event-free at 3 years and 47% and 38% were event-free at 5 years.

The investigators concluded: “There are several limitations of this [overall survival] analysis, including that it was not planned in the original protocol but instead was added after time-to-progression results were analyzed, and that not all patients participated in additional [overall survival] follow-up. However, the present results suggest fulvestrant 500 mg extends [overall survival] versus anastrozole.” A phase III trial comparing fulvestrant and anastrozole in hormonal therapy-naive patients with advanced breast cancer is under way.

Matthew J. Ellis, MD, of Baylor College of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by AstraZeneca. For full disclosures of the study authors, visit

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