FALCON: A phase III randomised trial of fulvestrant 500 mg vs. anastrozole for hormone receptor-positive advanced breast cancer

Background

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.

Methods

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.

Results

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.

Conclusions

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

AstraZeneca

Funding

AstraZeneca

Disclosure

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.