The addition of fulvestrant—which downgrades the estrogen receptor—to the aromatase inhibitor anastrozole enhances progression-free survival (PFS) and overall survival (OS) in postmenopausal women with hormone-receptor (HR)-positive metastatic breast cancer compared with anastrozole monotherapy, according to results of a new study (Mehta RS, et al. N Engl J Med. 2012;367:435-444).
The Southwest Oncology Group (SWOG) study randomized 707 postmenopausal patients with previous-ly untreated HR-positive metastatic breast cancer to anastrozole alone (N = 345) or to a combination of anastrozole plus fulvestrant (N = 349). All patients received 1 mg of anastrozole; those in the combination therapy group also received a 500-mg loading dose of fulvestrant on day 1, followed by 250 mg on days 14 and 28, and every 28 days thereafter. Patients in the anastrozole-alone group whose disease progressed were strongly encouraged to cross over to receive fulvestrant alone. Early in 2011, when the higher group (500 mg) of fulvestrant was approved by the US Food and Drug Administration (FDA), all patients were allowed to receive the 500-mg dose as well.
In the SWOG study, the median PFS was 15.0 months with the combination therapy and 13.5 months with anastrozole alone, representing a significant difference (P = .007); the OS was 41.3 months with anastrozole alone and 47.7 months with the combination therapy, also a significant difference (P = .049), even though 41% of these patients crossed over to fulvestrant after progression. This is the first study of first-line hormone therapy used for HR-positive metastatic breast cancer that shows an improvement in OS, not just PFS. It is also the first study to show the superiority of concurrent therapy with 2 hormonal modulators over monotherapy, especially an improvement in OS.
Toxic effects were mild and similar between the 2 groups. However, more patients who received the combination therapy discontinued treatment because of toxicity.
