The optimum endocrine treatment for postmenopausal women with advanced hormone-receptor-positive breast cancer that has progressed on non-steroidal aromatase inhibitors (NSAIs) is unclear. Several combinations of hormonal agents have been assessed in such patients with no consistent improvement in either time to progression of disease or survival.
In The Lancet Oncology, researchers report results of the phase III SoFEA trial trial in 723 postmenopausal women with hormone-receptor-positive breast cancer who had relapsed or progressed while receiving a NSAI. They were randomised to receive fulvestrant (FV 500 mg IM injection on day 1, followed by 250 mg doses on days 15 and 29, and then every 28 days) plus daily oral anastrozole 1 mg (n=243); FV plus anastrozole-matched placebo (n= 231); or daily oral exemestane 25 mg (n=249). The primary endpoint was progression-free survival (PFS).
According to the intention to treat analyses, median PFS was 4.4 months in patients on FV plus anastrozole, 4.8 months in those on FV plus placebo, and 3.4 months in those on exemestane. There was no difference between the patients on FV plus anastrozole and FV plus placebo (hazard ratio 1.00, 95% CI, 0.83 to 1.21; p=0.98), or between those on FV plus placebo and exemestane (0.95, 0.79 to 1.14; p=0.56). A total of 87 serious adverse events were reported: 36 in patients on FV plus anastrozole, 22 on FV plus placebo, and 29 on exemestane. Grade 3—4 adverse events were rare; the most frequent were arthralgia (3 FV plus anastrozole; 7 FV plus placebo; 8 exemestane), lethargy (3; 11; 11), and nausea or vomiting (5,2,8).
A couple of other phase 3 studies of anastrozole and FV have reported conflicting findings thus there remains no consistent data to support the suggestion that combination endocrine therapy is superior to treatment with one agent in early or advanced breast cancer.
According to an accompanying Commentary “a combination of endocrine agents with different mechanisms of action will probably not result in a meaningful improvement in outcomes for patients with breast cancer. Sequential use of endocrine agents remains the standard of care in patients with advanced breast cancer.”
Currently FV is licensed at a dose of 500 mg at intervals of one month, with an additional 500 mg dose given two weeks after the initial dose, for the treatment of postmenopausal women with oestrogen receptor positive, locally advanced or metastatic breast cancer for disease relapse on or after adjuvant anti-oestrogen therapy, or disease progression on therapy with an anti-oestrogen. In guidance issued in 2011, NICE did not support the use of FV, within its licensed indication, as an alternative to aromatase inhibitors.