The recently completed international, randomized, double-blind phase 3 FALCON trial demonstrated that fulvestrant improves outcomes in women with hormone receptor (HR)-positive, locally advanced, or metastatic breast cancer. Patients who received fulvestrant had a significantly longer period of progression-free survival (PFS), the primary end point of the trial, compared with those randomized to receive anastrozole.
Aromatase inhibitors (AIs) have long been a standard of care for patients with HR-positive locally advanced or metastatic breast cancer. A team of international investigators compared the efficacy of fulvestrant with that of anastrozole, a third-generation AI. They sought to determine whichdrug offered the greatest improvement in PFS in postmenopausal patients who had not received previous endocrine therapy.
Fulvestrant has been available since 2002 as a second-line treatment for postmenopausal women with metastatic, hormone-dependent breast cancer. It is also used in combination with palbociclib to treat HR-positive metastatic breast cancer in postmenopausal women with disease progression. The anastrozole plus palbociclib combination is also used in patients who have HR-positive/HER2-negative advanced breast cancer and who experience disease progression after endocrine therapy.
Based on the results of the FALCON trial, its investigators have suggested that fulvestrant be the new standard of care as first-line treatment for patients with HR-positive advanced breast cancer, supplanting anastrozole.
“The results of the FALCON study support the notion that a selective estrogen receptor degrader is a more efficacious treatment than a third-generation aromatase inhibitor, which is the standard of care in first-line endocrine therapy for patients with HR-positive advanced breast cancer,” wrote John F.R. Robertson, MD, Professor of Surgery, Faculty of Medicine & Health Sciences, at the University of Nottingham, Derby, UK, and colleagues. “These findings consolidate the known clinical effectiveness of fulvestrant and support the use of fulvestrant monotherapy in endocrine-naïve patients with HR-positive breast cancer.”
The investigators wrote that fulvestrant “is a preferred treatment option for patients with hormone receptor-positive locally advanced or metastatic breast cancer who have not received previous endocrine therapy.”
The FALCON trial included 462 patients who were recruited based on whether they had histologically confirmed estrogen receptor–positive or progesterone receptor–positive, or both, locally advanced or metastatic breast cancer. To be eligible, patients must have never received endocrine therapy, must have had a World Health Organization performance status of 0 to 2, and must have had ≥1 measurable or nonmeasurable lesions.
Eligible patients were randomly assigned to fulvestrant, 500 mg given by intramuscular injection, on days 0, 14, and 28, then every 28 days thereafter; or anastrozole, 1 mg orally daily, using a computer-generated randomization scheme.
Intervention by surgery or radiotherapy because of disease deterioration, or death from any cause were assessed in the intention-to-treat population. Safety outcomes were assessed in all patients who received ≥1 doses of randomized treatment (including placebo).
PFS was found to be significantly longer in the fulvestrant group than in the anastrozole group. Median PFS was 16.6 months in the fulvestrant group versus 13.8 months in the anastrozole group (hazard ratio [HR], 0.797; P = .0486).
Median overall survival could not be calculated because of insufficient follow-up time. At data cutoff, 67 (29%) of 230 patients in the fulvestrant group and 75 (32%) of 232 patients in the anastrozole group had died (HR, 0.88; P = .4277).
The authors noted that patients who achieved clinical response to fulvestrant had a longer duration of response than with anastrozole. “Thus, patients with endocrine-sensitive disease might not always require a combination treatment that is associated with greater toxicity,” they wrote.
The most common adverse events were arthralgia (17% in the fulvestrant group vs 10% in the anastrozole group) and hot flush (11% in the fulvestrant group vs 10% in the anastrozole group). Sixteen (7%) of 228 patients in the fulvestrant group and 11 (5%) of 232 patients in the anastrozole group discontinued therapy because of adverse events.
Updated data from FALCON presented at the 2016 San Antonio Breast Cancer Symposium showed a decreased risk for disease progression by 41% (HR, 0.592) with fulvestrant in patients whose disease has not spread to organs within the chest or abdomen (defined as nonvisceral disease) compared with anastrozole. In this subgroup, median PFS was 22.3 months in fulvestrant-treated patients versus 13.8 months in anastrozole-treated patients. In those with visceral disease, the treatment effect was comparable with fulvestrant and anastrozole (HR, 0.993).
Robertson JFR, Bondarenko IM, Trishkina E, et al. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016;388:2997-3005.
Robertson JFR, Noguchi S, Shao Z, et al. Progression-free survival results in patient subgroups from a phase 3 randomized trial of fulvestrant 500 mg vs anastrozole for hormone receptor-positive advanced breast cancer (FALCON) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX. Philadelphia, PA: AACR; Cancer Res. 2017;77(4 Suppl):Abstract P2-08-02.