Fulvestrant Tops Anastrozole in ER-Positive Breast Cancer
Copenhagen, Denmark—A novel approach to targeting the estrogen receptor (ER) led to improved progression-free survival (PFS) in postmenopausal women with advanced, hormone receptor (HR)-positive breast cancer, according to data from the FALCON clinical trial that were reported at the 2016 European Society for Medical Oncology Congress.
Patients who received the selective ER degrader fulvestrant (Faslodex) had a median PFS of 16.6 months compared with 13.8 months for patients who received the aromatase inhibitor anastrozole (Arimidex). The benefit persisted across a subgroup analysis but appeared to be driven by a large effect in patients without visceral metastases, said Matthew Ellis, MD, PhD, Director of the Breast Center Baylor College of Medicine, Houston, TX, who presented the study results.
“The primary analysis was supported by secondary efficacy end points. Treatment effects were largely consistent across prespecified patient subgroups, with the largest treatment effect seen in patients without visceral disease,” Dr Ellis said. “The adverse event profile was generally consistent with known profiles. Health-related quality of life was maintained and was similar in both treatment groups.”
The current treatment recommendations specify a third-generation aromatase inhibitor or tamoxifen for postmenopausal patients with HR-positive advanced or metastatic breast cancer. The phase 2 FIRST clinical trial established that fulvestrant is at least equivalent to anastrozole in this patient population (Robertson JF, et al. J Clin Oncol. 2009;27:4530-4535).
The FALCON Clinical Trial
The FIRST study provided the rationale for the phase 3 FALCON clinical trial, which was designed to be a definitive comparison of fulvestrant and anastrozole in postmenopausal women with locally advanced or metastatic HR-positive breast cancer that was not exposed to endocrine therapy. Patients were randomized to receive fulvestrant 500 mg daily or anastrozole 1 mg daily. The primary end point was PFS.
The primary analysis showed that patients who received fulvestrant had a 20% reduction in the risk for disease progression or death (P = .0486). A subgroup analysis failed to identify any patients who benefited more from treatment with anastrozole than with fulvestrant, including patients with locally advanced or metastatic breast cancer, the use of previous chemotherapy, geographic region, ER and progesterone receptor status, and bisphosphonate use.
The only exception to the beneficial effect of fulvestrant involved women with visceral metastases, who had similar PFS with anastrozole as with fulvestrant. Conversely, patients without visceral metastases had a 41% hazard reduction with fulvestrant.
Overall, survival did not differ between the treatment groups, but Dr Ellis noted that overall survival maturity was 31% at the median follow-up of 25 months.
The examination of other secondary end points yielded mixed results. The objective response rate did not differ substantially (46.1% with fulvestrant vs 44.9% with anastrozole), nor did the clinical benefit rate (78.3% with fulvestrant vs 74.1% with anastrozole). The median duration of response favored fulvestrant (20 months) over anastrozole (13.2 months), but the median duration of clinical benefit was similar between the treatment arms (22.1 months vs 19.1 months, respectively). The time to deterioration in quality of life also did not differ substantially between fulvestrant and anastrozole (13.8 months vs 11.1 months, respectively).
The safety analysis showed similar rates of adverse events between fulvestrant (72.8%) and anastrozole (74.6%), overall, including arthralgia (16.7% vs 10.3%, respectively), hot flushes (11.4% vs 10.3%), nausea (10.5% vs 10.3%), and fatigue (11.4% vs 8.9%).
Serious adverse event rates were 13.2% versus 13.4% in the fulvestrant versus anastrozole groups, respectively. Dr Ellis reported that 7% of patients who received fulvestrant discontinued treatment because of adverse events versus 4.7% of patients who received anastrozole.
“These results…confirm that fulvestrant is more efficacious than anastrozole in postmenopausal women with hormone receptor–positive, locally advanced or metastatic breast cancer who have not received previous endocrine therapy,” Dr Ellis concluded.