In the international phase III FALCON trial reported in The Lancet, Robertson et al found that progression-free survival was improved with intramuscular fulvestrant (Faslodex) vs oral anastrozole in endocrine therapy–naive women with hormone receptor–positive locally advanced or metastatic breast cancer.
In the double-blind trial, 462 patients from 113 sites in 20 countries in Asia, Europe, North America, South America, and South Africa were randomized between October 2012 and July 2014 to receive fulvestrant (n = 230) or anastrozole (n = 232). Fulvestrant was given as 500 mg intramuscular injections on days 0, 14, 28, and every 28 days thereafter; anastrozole was given at 1 mg orally daily. The primary endpoint was progression-free survival in the intent-to-treat population.
For the fulvestrant and anastrozole groups: median age was 64 and 62 years (47% and 39% ≥ 65 years); 76% and 75% were white and 16% and 15% were Asian; time from diagnosis was at least 1 year for 30% and 29%; 76% and 77% had estrogen receptor– and progesterone receptor–positive disease; 88% and 86% had metastatic disease; 59% and 51% had visceral disease; 84% and 84% had measureable disease; 16% and 19% had received chemotherapy for locally advanced or metastatic disease; and 23% and 22% had received radiotherapy.
Median progression-free survival was 16.6 months (95% confidence interval [CI] = 13.83–20.99 months) in the fulvestrant group vs 13.8 months (95% CI = 11.99–16.59 months) in the anastrozole group (hazard ratio [HR] = 0.797, P = .0486). Among patients with measurable disease, objective response was observed in 46% (89/193) of fulvestrant patients and 45% (88/196) of anastrozole patients (odds ratio = 1.07, P = .7290); median duration of response was 20.0 months vs 13.2 months.
The magnitude of progression-free survival benefit with fulvestrant was consistent across most prespecified subgroups, except for patients with previous chemotherapy for locally advanced or metastatic disease, patients with nonmeasurable disease, patients who were not estrogen receptor– and progesterone receptor–positive, and patients with visceral disease. For example, hazard ratios were 0.59 (95% CI = 0.42–0.84; median progression-free survival was 22.3 vs 13.8 months) among patients with nonvisceral disease and 0.99 (95% CI = 0.74–1.33; median progression-free survival = 13.8 vs 15.9 months) among those with visceral disease (post-hoc interaction test P = .0092). Median overall survival could not yet be calculated. At data cutoff, death had occurred in 29% of the fulvestrant group vs 32% of the anastrozole group (HR = 0.88, P = .4277).
The most common adverse events of any grade were arthralgia (17% in the fulvestrant group vs 10% in the anastrozole group) and hot flushes (11% vs 10%). Grade ≥ 3 adverse events occurred in 22% vs 18%, with none occurring in > 5% of either group. Serious adverse events occurred in 13% vs 13%. Adverse events of special interest—ie, joint disorders and back pain—occurred in 26% vs 18%. Adverse events led to discontinuation of treatment in 7% vs 5%. Adverse events led to death in 3% of each group, with none of the deaths considered related to study treatment.
The authors concluded: “Fulvestrant has superior efficacy and is a preferred treatment option for patients with hormone receptor-positive locally advanced or metastatic breast cancer who have not received previous endocrine therapy compared with a third-generation aromatase inhibitor, a standard of care for first-line treatment of these patients.”
The study was funded by AstraZeneca.
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