Abstract PD5-09: Fulvestrant for hormone receptor-positive advanced breast cancer in patients with visceral vs non-visceral metastases: Findings from FALCON, FIRST, and CONFIRM
Authors: Roberston JFR , Di Leo A , Fazal M , Lichfield J , Ellis MJ 
Published: February 2018

Abstract
BACKGROUND
Patients with hormone receptor-positive (HR+) locally advanced or metastatic breast cancer (LA/MBC) and non-visceral metastases (non-VM) generally have a better prognosis than patients with visceral metastases (VM). However, in the absence of visceral crisis, endocrine therapy (ET) remains an effective treatment option in both patient groups. This descriptive analysis examined the treatment effect of fulvestrant 500 mg vs comparators in postmenopausal patients with HR+ LA/MBC, with or without VM.
METHODS
Three randomized studies of fulvestrant 500 mg for postmenopausal HR+ LA/MBC were included. The Phase 3 FALCON study (NCT01602380) compared fulvestrant 500 mg with anastrozole in patients without any prior ET (n=462; fulvestrant 500 mg: 58.7% with VM; anastrozole: 51.3% with VM). The Phase 2 FIRST study (NCT00274469) compared fulvestrant 500 mg with anastrozole in patients who had not received ET for advanced disease (n=205; fulvestrant 500 mg: 47.1% with VM; anastrozole: 56.3% with VM). The Phase 3 CONFIRM study (NCT00099437) compared fulvestrant 500 mg with fulvestrant 250 mg (n=736; fulvestrant 500 mg: 56.6% with VM; fulvestrant 250 mg: 52.9% with VM); patients had received prior ET for adjuvant/advanced disease. The treatment effect of fulvestrant 500 mg vs comparator ET was determined using log-rank tests.
RESULTS
In FALCON, there was a greater treatment effect with fulvestrant 500 mg vs anastrozole for progression-free survival (PFS) in the non-VM group (hazard ratio [HR] 0.59) vs the VM group (HR 0.99). A consistent treatment effect was observed for fulvestrant 500 mg vs comparator for PFS in FIRST (non-VM HR 0.58; VM HR 0.82) and CONFIRM (non-VM HR 0.72; VM HR 0.86). Median PFS of fulvestrant 500 mg vs comparator in non-VM and VM subgroups was: 22.3 months (m) vs 13.8 m and 13.8 m vs 15.9 m, respectively, in FALCON; 34.0 m vs 21.3 m and 9.8 m vs 9.9 m in FIRST; and 10.4 m vs 5.9 m and 4.7 m vs 4.0 m in CONFIRM.
Clinical benefit rate with fulvestrant 500 mg vs anastrozole in FALCON was 87.4% vs 75.2% in the non-VM group, and 71.9% vs 73.1% in the VM group.
Overall survival (OS) in FALCON (31% maturity) showed a greater treatment effect with fulvestrant 500 mg vs anastrozole in the non-VM group vs the VM group (HR 0.60 vs 1.09). In terms of OS, in FIRST there was a greater treatment effect with fulvestrant 500 mg vs anastrozole in the non-VM group compared with the VM group (HR 0.68 vs 0.86). In CONFIRM, improved OS was observed with fulvestrant 500 mg vs fulvestrant 250 mg; this treatment effect was consistent in non-VM (HR 0.78) and VM subgroups (HR 0.83).
CONCLUSIONS
In three studies, an improved treatment effect of fulvestrant 500 mg vs comparator ET for HR+ LA/MBC was observed in patients with non-VM. The treatment effect of fulvestrant 500 mg vs comparator for PFS across all three studies appeared consistent. A reduced treatment effect of fulvestrant 500 mg vs comparator was generally seen in patients with VM, although fulvestrant 500 mg was still as effective as, or slightly more effective than, the comparator. These data suggest that patients without VM may benefit more from fulvestrant 500 mg than patients with VM.
Citation Format: Roberston JFR, Di Leo A, Fazal M, Lichfield J, Ellis MJ. Fulvestrant for hormone receptor-positive advanced breast cancer in patients with visceral vs non-visceral metastases: Findings from FALCON, FIRST, and CONFIRM [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD5-09.