No Additional Benefit of Double Endocrine Treatment After Progression on Aromatase Inhibitors in Advanced Hormone Receptor–Positive Breast Cancer
In the SoFEA trial, reported in Lancet Oncology by Stephen R.D. Johnston, PhD, FRCP, of Royal Marsden NHS Foundation Trust, and colleagues, postmenopausal women with advanced hormone receptor–positive breast cancer that progressed on nonsteroidal aromatase inhibitors were treated with the steroidal antiestrogen fulvestrant (Faslodex) with or without anastrozole or with exemestane alone. The study found no additional benefit of fulvestrant plus anastrozole treatment.
Study Details
In this composite phase III trial performed in the United Kingdom and South Korea, postmenopausal women with hormone receptor–positive breast cancer (estrogen or progesterone receptor–positive or both) were eligible if they had relapsed or progressed with locally advanced or metastatic disease on a nonsteroidal aromatase inhibitor (given as adjuvant for at least 12 months or as first-line treatment for at least 6 months). A total of 723 patients were randomly assigned to intramuscular fulvestrant at 500 g on day 1 followed by 250 mg on days 15 and 29 and then every 28 days plus daily oral anastrozole at 1 mg (n = 243), fulvestrant plus anastrozole-matched placebo (n = 231), or daily oral exemestane at 25 mg (n = 249). Patients and investigators were aware of assignment to fulvestrant or exemestane but not of assignment to anastrozole or placebo. The primary endpoint was progression-free survival.
Outcomes
After a median follow-up of 37.9 months, median progression-free survival was 4.4 months in the fulvestrant/anastrozole group, 4.8 months in the fulvestrant/placebo group, and 3.4 months in the exemestane group. There was no significant difference in progression-free survival between the fulvestrant/anastrozole group and the fulvestrant/placebo group (hazard ratio [HR] = 1.00, P = .98) or between the fulvestrant/placebo group and the exemestane group (HR = 0.95, P = .56). There was no significant difference in median overall survival between the fulvestrant/anastrozole group (20.2 months) and the fulvestrant/placebo group (19.4 months) or between the fulvestrant/placebo group and the exemestane group (21.6 months).
Serious adverse events occurred in 15% of the fulvestrant/anastrozole group, 10% of the fulvestrant/placebo group, and 12% of the exemestane group. Grade 3 or 4 adverse events were rare, with only lethargy occurring in 5% or more of any treatment group (5% in both the fulvestrant/placebo and exemestane groups).
The investigators concluded, “After loss of response to [nonsteroidal aromatase inhibitors] in postmenopausal women with hormone receptor-positive advanced breast cancer, maximum double endocrine treatment with 250 mg fulvestrant combined with estrogen deprivation is no better than either fulvestrant alone or exemestane.”
The study was funded by Cancer Research UK and AstraZeneca.
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