Sean Bohen, MD, PhD
Frontline treatment with fulvestrant (Faslodex) improved progression-free survival (PFS) versus anastrozole for postmenopausal patients with locally-advanced or metastatic HR-positive breast cancer, according to topline findings from the phase III FALCON trial that were announced by AstraZeneca, the company developing the hormonal therapy.
PFS was the primary endpoint of the FALCON study, which enrolled 524 patients to receive fulvestrant at 500 mg or anastrozole at 1 mg. Safety profiles were consistent with expectations for each medication in the trial. Full data from the trial have not yet been released and are being prepared for presentation at an upcoming medical meeting, according to AstraZeneca.
“The FALCON results bring us closer to offering more and earlier treatment options to postmenopausal women with HR+ locally-advanced or metastatic breast cancer; the potential to delay disease progression is important for these patients as there is currently no cure,” Sean Bohen, MD, PhD, executive vice president, Global Medicines Development and Chief Medical Officer at AstraZeneca, the company developing fulvestrant, said in a statement.
Secondary endpoints of the study, which are still being assessed, included overall survival (OS), objective responses rate (ORR), and safety. Additionally, the trial, which was launched in 2012, was designed to compare health-related quality of life, duration of clinical benefit, and other response-specific endpoints.
Prior to the phase III trial, the open-label phase II FIRST study compared frontline fulvestrant with anastrozole for postmenopausal women with HR-positive metastatic breast cancer. In this trial, treatment with 500-mg fulvestrant reduced the risk of death by 30% compared with 1-mg anastrozole, according to findings presented at the 2014 San Antonio Breast Cancer Symposium.
In the phase II open-label study, postmenopausal patients with ER-positive primary breast cancer were randomized to receive fulvestrant at 500 mg on day 0, 14, and 28 followed by every 28 days (n = 102) or continuous anastrozole at 1 mg (n = 103). Patients who received prior adjuvant therapy were permitted to enroll in the trial. The median age of patients was 67 years.
The primary endpoint of the study was clinical benefit rate (CBR), defined as objective response or stable disease for ≥24 weeks. Secondary outcome measures focused on ORR and time to progression (TTP). OS was not defined as an original endpoint of the study.
The median OS was 54.1 months with fulvestrant compared with 48.4 months with anastrozole (HR, 0.70; 95% CI, 0.50-0.98; P
= .041). Additionally, the benefit was seen across predefined subgroups of patients by age, tumor size, prior treatments, and other stratification factors.
An earlier analysis of the study revealed a 72.5% CBR with fulvestrant compared with 67% for anastrozole (odds ratio, 1.30; P
= .386). The ORR was 36% with fulvestrant and 35.5% with anastrozole. The TTP with fulvestrant was 23.4 versus 13.1 months with anastrozole (HR, 0.66; 95% CI, 0.47-0.92; P
Serious adverse events (AEs) in the trial were similar between fulvestrant (23.8%) and anastrozole (21.4%). The incidence of AEs coincided with the known toxicity profiles for both agents.
“Fulvestrant has over 10 years of clinical evidence and we are committed to exploring its potential along with the rest of our outstanding oncology portfolio,” said Bohen.
The FDA initially approved fulvestrant in 2002, at a lower 250-mg dose. At the 500 mg dose, the agent is currently approved for postmenopausal women with HR+ metastatic breast cancer following antiestrogen therapy. In March 2016, fulvestrant was also approved in combination with palbociclib following endocrine therapy for women with HR-positive/HER2-negative breast cancer.
Robertson JFR, Llombart-Cussac A, Feltl D, et al. Fulvestrant 500 mg versus anastrozole as first-line treatment for advanced breast cancer: overall survival from the phase II ‘first’ study. Presented at: 2014 San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, TX. Abstract S6-04.