Fulvestrant Yields No OS Differences Vs Anastrozole in HR+ Breast Cancer

There remains a high unmet need for a novel [selective estrogen receptor degrader] that further improves convenience via oral dosing, addresses [endocrine therapy] resistance, and provides broader efficacy across clinically relevant patient subgroups,” according to the study authors.

No significant differences in overall survival (OS) outcomes occurred with fulvestrant (Faslodex) compared with anastrozole (Arimidex) in the treatment of patients who are postmenopausal with endocrine therapy–naïve, hormone receptor (HR)–positive, advanced breast cancer, according to final OS data from the phase 3 FALCON trial (NCT01602380) published in The Journal of Clinical Oncology.¹

With a median follow-up of 37.1 months and 68% maturity, the median OS was 44.8 months (95% CI, 37.8-57.6) with fulvestrant vs 42.7 months (95% CI, 36.6-50.1) with anastrozole (HR, 0.97; 95% CI, 0.77-1.21; P = .76). Although OS outcomes were consistent across most subgroups, investigators noted a trend towards improved survival with fulvestrant among those with nonvisceral disease; the median OS was 65.2 months vs 47.8 months in each respective arm (HR, 0.85; 95% CI, 0.60-1.20). Among patients with visceral disease, the median OS was 37.2 months vs 40.7 months, respectively (HR, 1.06; 95% CI, 0.80-1.42).

Post hoc exploratory analysis data showed that the median OS with fulvestrant was 65.2 months in the nonvisceral disease subgroup vs 37.2 months in the visceral disease subgroup (HR, 0.62; 95% CI, 0.45-0.85). The median OS with anastrozole was 47.8 months and 40.7 months in each patient subgroup (HR, 0.78; 95% CI, 0.57-1.07).

“There remains a high unmet need for a novel [selective estrogen receptor degrader] that further improves convenience via oral dosing, addresses [endocrine therapy] resistance, and provides broader efficacy across clinically relevant patient subgroups,” John F.R. Robertson, PhD, a professor of Surgery in the Faculty of Medicine and Health Sciences, and director of the Centre of Excellence for Autoimmunity in Cancer at The University of Nottingham, wrote with study coauthors.¹ “Several candidates have entered late-stage development with mixed results. Elacestrant [Orserdu] is approved for postmenopausal patients with estrogen receptor–positive/HER2-negative, [ESR1-mutated advanced breast cancer] that has progressed following [at least 1] line of [endocrine therapy].”²

In the double-blind, parallel-group, multicenter phase 3 FALCON study, patients were randomly assigned to receive fulvestrant (n = 230) at 500 mg intramuscularly on days 1, 14, 28, and every 28 days thereafter or fulvestrant (n = 232) at 1 mg orally each day.³

The trial’s primary end point was progression-free survival. Secondary end points included OS, objective response rate, duration of response, clinical benefit rate, and health-related quality of life (HRQOL).

Patients 18 years and older who were postmenopausal with histologically confirmed breast cancer, positive HR status of primary or metastatic tumor tissue, locally advanced or metastatic disease, and at least 1 measurable lesion were eligible for enrollment on the trial.

Across the intent-to-treat population, the median age was 64 years (range, 38-87) in the fulvestrant arm and 62 years (range, 36-90) in the anastrozole arm. In each respective 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%).

Treatment discontinuation for any reason was reported in 94.7% of the fulvestrant arm and 95.7% of the anastrozole arm. Investigators highlighted subsequent therapy use in 49.1% of both groups, with the most common treatments in each respective arm including exemestane (Aromasin; 14.8% vs 21.6%), radiotherapy (13.5% vs 12.5%), and capecitabine (Xeloda; 11.3% vs 14.2%).

Serious adverse effects (SAEs) occurred in 17.1% and 15.5% of patients who received fulvestrant and anastrozole, respectively. Treatment-related SAEs affected 2.2% and 1.3% of patients in each arm. Overall, investigators observed no new safety signals.

Regarding HRQOL, data showed no significant differences in time to deterioration of Functional Assessment of Cancer Therapy – Breast total scores (HR, 0.82; 95% CI, 0.66-1.03; P = .08) or Trial Outcome Index (HR, 0.88; 95% CI, 0.70-1.11; P = .28) between the treatment arms. Investigators advised caution when interpreting these outcomes based on variance in questionnaire compliance over time.

References

1. Robertson JFR, Shao Z, Noguchi S, et al. Fulvestrant versus anastrozole in endocrine therapy–naive women with hormone receptor–positive advanced breast cancer: final overall survival in the phase III FALCON trial. J Clin Oncol. Published online January 7, 2025. doi:10.1200/JCO.24.00994
2. FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. News release. FDA. January 27, 2023. Accessed January 21, 2025. bit.ly/3kQrxHq
3. A global study to compare the effects of fulvestrant and Arimidex in a subset of patients with breast cancer. (FALCON). ClinicalTrials.gov. Updated November 27, 2024. Accessed January 21, 2025. https://tinyurl.com/27e86u24