Final overall survival (OS) data from the phase 3 FALCON trial indicates that fulvestrant did not significantly improve OS compared to anastrozole in postmenopausal patients with endocrine therapy–naive, hormone receptor (HR)–positive, advanced breast cancer. The findings, published in The Journal of Clinical Oncology, highlight the ongoing need for novel therapies in this patient population.
The multinational, double-blind FALCON study randomly assigned 462 patients to receive either fulvestrant (n = 230) or anastrozole (n = 232). While earlier analysis demonstrated a progression-free survival benefit with fulvestrant, the final OS analysis, triggered after a median follow-up of 37.1 months and 68% data maturity, revealed no statistically significant difference between the two treatments.
Overall Survival Results
The median OS was 44.8 months (95% CI, 37.8-57.6) in the fulvestrant arm compared to 42.7 months (95% CI, 36.6-50.1) in the anastrozole arm, with a hazard ratio of 0.97 (95% CI, 0.77-1.21; P = .7579). These results suggest that, overall, fulvestrant did not provide a significant survival advantage over anastrozole in this patient population.
Subgroup Analysis
Interestingly, subgroup analysis revealed a trend towards improved survival with fulvestrant among patients with nonvisceral disease. In this subgroup, the median OS was 65.2 months with fulvestrant compared to 47.8 months with anastrozole (HR, 0.85; 95% CI, 0.60-1.20). Conversely, in patients with visceral disease, the median OS was 37.2 months and 40.7 months for fulvestrant and anastrozole, respectively (HR, 1.06; 95% CI, 0.80-1.42).
Post hoc exploratory analyses further emphasized this difference, showing a greater improvement in OS with fulvestrant in patients with nonvisceral versus visceral disease (median 65.2 vs 37.2 months; HR, 0.62; 95% CI, 0.45-0.85) compared to anastrozole (median 47.8 vs 40.7 months; HR, 0.78; 95% CI, 0.57-1.07).
Expert Commentary
According to John F.R. Robertson, PhD, Professor of Surgery at the University of Nottingham and a study author, there remains a significant unmet need for novel selective estrogen receptor degraders (SERDs) that offer improved convenience through oral dosing, address endocrine therapy resistance, and provide broader efficacy across clinically relevant patient subgroups. He noted that while several candidates are in late-stage development, results have been mixed. Elacestrant has been approved for postmenopausal patients with estrogen receptor–positive/HER2-negative, ESR1-mutated advanced breast cancer that has progressed following at least one line of endocrine therapy.
Trial Design and Patient Characteristics
The FALCON trial enrolled postmenopausal women aged 18 years or older with histologically confirmed breast cancer, positive HR status, and locally advanced or metastatic disease. The primary endpoint was progression-free survival, while secondary endpoints included OS, objective response rate, duration of response, clinical benefit rate, and health-related quality of life.
The median age of patients was 64 years in the fulvestrant arm and 62 years in the anastrozole arm. Most patients were White (76% vs 75%), had a World Health Organization performance status of 0 (51% vs 50%), metastatic disease (88% vs 86%), and visceral disease (59% vs 51%).
Safety and Tolerability
Serious adverse events (SAEs) occurred in 17.1% and 15.5% of patients receiving fulvestrant and anastrozole, respectively. Treatment-related SAEs affected 2.2% and 1.3% of patients in each arm. No new safety signals were identified.
