This Phase III, randomised, double-blind, multicentre trial (FALCON; NCT01602380) compared the selective estrogen receptor (ER) degrader (SERD) fulvestrant with anastrozole in patients with ER- and/or progesterone receptor-positive locally advanced or metastatic breast cancer who had not received prior hormonal therapy.
Patients were randomised 1:1 to fulvestrant (500 mg IM on Days 0, 14, 28, then each 28 days) or anastrozole (1 mg daily). The primary endpoint was progression-free survival (PFS), assessed via RECIST 1.1, surgery/radiotherapy for disease worsening, or death. Secondary endpoints were: overall survival (OS); objective response rate (ORR, complete response [CR] or partial response [PR]); duration of response (DoR); expected DoR (EDoR); clinical benefit rate (CBR; CR, PR, or stable disease ≥24 weeks); duration of clinical benefit (DoCB); expected DoCB (EDoCB); health-related quality of life (HRQoL); and safety.
In total, 462 patients (fulvestrant, n = 230; anastrozole, n = 232) were randomised. The primary endpoint was met as shown by a statistically significant improvement in PFS with fulvestrant vs. anastrozole (hazard ratio 0.797 [95% confidence interval 0.637, 0.999]; p = 0.0486; median PFS, 16.6 vs. 13.8 months, respectively). Secondary outcomes are shown in the Table (OS maturity was 31% at a median follow-up of 25.0 months). Treatment impact on HRQoL was similar in both treatment groups. The most common adverse events were arthralgia (16.7% vs. 10.3%) and hot flushes (11.4% vs. 10.3%) for fulvestrant and anastrozole, respectively.
These results confirm the superior efficacy of fulvestrant over anastrozole in postmenopausal women with hormone receptor-positive locally advanced or metastatic breast cancer who have not received prior hormonal therapy.
Clinical trial identification
ClinicalTrials.gov identifier: NCT01602380
Legal entity responsible for the study
M.J. Ellis: Employment, leadership, stock or other ownership, patents, royalties or intellectual property - Bioclassifier LLC; Consulting or advisory role - AstraZeneca, Pfizer, Novartis, Celgene. K-L. Cheung: Honoraria, speakers bureau - Chugai: Research Funding–AstraZeneca. S. Noguchi: Honoraria, consulting or advisory role–AstraZeneca, Chugai, Nippon Kayaku, Novartis, Pfizer, Taiho; Research funding – AstraZeneca, Chugai, Nippon Kayaku, Novartis, Pfizer, Taiho, Takeda; Patents, royalties or intellectual property – Sysmex. L.M. Grinsted: Employment, stock or other ownership – AstraZeneca. M. Fazal: Employment – AstraZeneca. M. Stuart: Former employment, and current stock or other ownership – AstraZeneca; Current employment – Kingston Oncology Ltd. J.F. Robertson: Stock or other ownership – Oncimmune; Honoraria, consulting or advisory role, travel or expenses – AstraZeneca, Bayer AG; Research funding – AstraZeneca, Bayer AG, Novartis; Expert testimony – AstraZeneca. All other authors have declared no conflicts of interest.
|Secondary endpoint||Fulvestrant (N = 230)||Anastrozole (N = 232)|
|OS maturity (% deaths)||29.1%||32.3%||Hazard ratio (95% CI) 0.88 (0.63, 1.22); p = 0.428|
|ORR||46.1% [89/193]||44.9% [88/196]||Odds ratio (95% CI) 1.07 (0.72, 1.61); p = 0.729|
|Median DoR||20.0 months||13.2 months||-|
|EDoR||11.4 months||7.5 months||Ratio (95% CI) 1.52 (1.23, 1.89); p < 0.001|
|CBR||78.3% [180/230]||74.1% [172/232]||Odds ratio (95% CI) 1.25 (0.82, 1.93); p = 0.305|
|CR||3.0% [7/230]||3.4% [8/232]||-|
|PR||37.4% [86/230]||35.3% [82/232]||-|
|SD ≥24 weeks||37.8% [87/230]||35.3% [82/232]||-|
|Median DoCB||22.1 months||19.1 months||-|
|EDoCB||21.9 months||17.5 months||Ratio (95% CI) 1.26 (1.13, 1.39); p < 0.001|