Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study

Abstract

PurposeTo compare overall survival (OS) for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for advanced breast cancer.Patients and MethodsThe Fulvestrant First-Line Study Comparing Endocrine Treatments (FIRST) was a phase II, randomized, open-label, multicenter trial. Postmenopausal women with estrogen receptor–positive, locally advanced/metastatic breast cancer who had no previous therapy for advanced disease received either fulvestrant 500 mg (days 0, 14, 28, and every 28 days thereafter) or anastrozole 1 mg (daily). The primary end point (clinical benefit rate [72.5% and 67.0%]) and a follow-up analysis (median time to progression [23.4 months and 13.1 months]) have been reported previously for fulvestrant 500 mg and anastrozole, respectively. Subsequently, the protocol was amended to assess OS by unadjusted log-rank test after approximately 65% of patients had died. Treatment effect on OS across several subgroups was examined. Tolerability was evaluated by adverse event monitoring.ResultsIn total, 205 patients were randomly assigned (fulvestrant 500 mg, n = 102; anastrozole, n = 103). At data cutoff, 61.8% (fulvestrant 500 mg, n = 63) and 71.8% (anastrozole, n = 74) had died. The hazard ratio (95% CI) for OS with fulvestrant 500 mg versus anastrozole was 0.70 (0.50 to 0.98; P = .04; median OS, 54.1 months v 48.4 months). Treatment effects seemed generally consistent across the subgroups analyzed. No new safety issues were observed.ConclusionThere are several limitations of this OS 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 OS follow-up. However, the present results suggest fulvestrant 500 mg extends OS versus anastrozole. This finding now awaits prospective confirmation in the larger phase III FALCON (Fulvestrant and Anastrozole Compared in Hormonal Therapy Naïve Advanced Breast Cancer) trial (ClinicalTrials.gov identifier: NCT01602380).

Endocrine Therapeutic Strategies for Patients with Hormone Receptor-positive Advanced Breast Cancer

“…There is an apparent improvement in efficacy of fulvestrant in the patient group with non-visceral versus visceral disease in the FALCON trial (Figure 2), and similar observations were reported in the FIRST 65 and CONFIRM 24 trials. Current guidelines still recommend the use of endocrine therapy for visceral patients not in visceral crisis, however.…”

NCCN Guidelines Insights: Breast Cancer, Version 1.2017

“…82 The median OS was observed to be longer in the fulvestrant group than in the anastrozole group (54.1 vs 48.4 months; HR, 0.70; P=.041). 84 Results from a recent phase III trial (FALCON) of first-line treatment with fulvestrant compared with anastrozole in women with metastatic ERpositive breast cancer demonstrated improved PFS with fulvestrant (at the higher dose, 500 mg) over anastrazole at a median follow-up of 25.0 months (16.6 vs 13.8 months; HR for progression or death, 0.797; 95% CI, 0.637-0.999). 85 Quality-of-life outcomes were similar between the groups, with the most common adverse effects being arthralgia (17% vs 10%) and hot flashes (11% vs 10%) for fulvestrant and anastrazole, respectively.…”

Aromatase inhibitors of the third generation in endocrine therapy of breast cancer and endometrial cancer: the successes and failures of the combination therapy

“…В группе фулвестранта по сравнению с группой анастрозола было зарегистрировано увеличение медианы вре-мени до прогрессирования на 10,3 месяца (с 13,1 до 23,4 месяца), а также увеличение медианы об-щей выживаемости на 5,7 месяца (с 48,4 до 54,1 ме-сяца). При заключительном анализе установлено, что смертность составила 61,8 % (n = 63) в группе фульвестранта и 71,8 % (n = 74) в группе анастрозо-ла [40].…”