LUGANO-COPENHAGEN - Fulvestrant significantly increases progression-free survival in women with hormone-receptor-positive advanced breast cancer, particularly those with less aggressive lower-volume disease, researchers reported at the ESMO 2016 Congress in Copenhagen.
Fulvestrant is a selective estrogen receptor degrader that targets the function of the hormone receptor so, unlike aromatase inhibitors such as anastrozole, it does not interfere with estrogen levels themselves.
The randomized, double-blind, multi-center phase III trial enrolled 462 women with inoperable locally-advanced or metastatic ER-positive, HER-negative breast cancer, who had not received prior hormone therapy.
Half the patients (n=230) were randomized to 500mg intramuscular injections of fulvestrant (Days 0, 14, 28, then every 28 days), or to 1mg of anastrozole daily (n=232), and were also allowed one line of chemotherapy.
After a median follow-up of 25 months, patients treated with fulvestrant had a statistically significant 21% improvement in progression-free survival compared to those treated with anastrozole (16.6 months vs. 13.8 months, p = 0.048).
However subgroup analysis showed an even greater impact on progression-free survival in patients whose disease had not spread to the liver or lungs at baseline (22.3 vs. 13.8 months).
“For patients with non-visceral disease whose life isn’t immediately threatened by breast cancer – a group for whom physicians would typically choose endocrine therapy as a first approach – it looks like fulvestrant could be a new standard of care compared to anastrozole,” said the study’s principle investigator Dr. Matthew Ellis, from the Lester and Sue Smith Breast Center, Baylor College of Medicine in Houston, Texas, USA.
Both groups showed a similar health-related quality of life, and the most common adverse events were arthralgia (joint pain) (16.7% vs. 10.3%) and hot flushes (11.4% vs. 10.3%) for fulvestrant and anastrozole, respectively.
“It’s tolerated as well as anastrozole, and better than other drugs that could potentially be used in this setting such as chemotherapy or CDK4 inhibitors,” Ellis said.
“In patients for whom you are looking for a low toxicity approach, such as older patients or those with low volume disease, it looks like a good option.”
Researchers also observed a significantly greater duration of response to treatment in the fulvestrant group compared to the anastrozole group, which Ellis suggested could account for the increase in progression-free survival.
Commenting on the study, Dr Nicholas Turner, team leader at the Institute of Cancer Research and Medical Oncologist at the Royal Marsden, London, UK, said the results represent an important advance in the treatment of the most common form of breast cancer, and suggest a potential benefit for using fulvestrant earlier in a patient’s treatment.
“However two factors complicate moving this new finding into routine clinical practice: firstly, the study only included patients with no prior hormone treatment yet many patients presenting with advanced breast cancer have previously been treated for the primary breast cancer,” Turner said.
“Secondly, since the design of the study, the standard of care for these women has moved on, with the CDK4/6 inhibitor palbociclib now licensed in US, in combination with an aromatase inhibitor, for the same group of patients. Further studies will help define the most optimal sequence of therapy for women with advanced breast cancer.”
Notes to Editors
Abstract LBA14_PR - FALCON: a phase III randomised trial of fulvestrant 500 mg vs. anastrozole for hormone receptor-positive advanced breast cancer ‘, will be presented by Dr Matthew Ellis during the Proffered Paper Session, Metastatic Breast Cancer on Saturday 8 October, 11:00 to 12:30 (CEST) in Room Vienna.
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Abstract for LBA14_PR
FALCON: A phase III randomised trial of fulvestrant 500 mg vs. anastrozole for hormone receptor-positive advanced breast cancer
M.J. Ellis1, I. Bondarenko2, E. Trishkina3, M. Dvorkin4, L. Panasci5, A. Manikhas6, Y. Shparyk7, S. Cardona-Huerta8, K-L. Cheung9, M.J. Philco-Salas10, M. Ruiz-Borrego11, Z. Shao12, S. Noguchi13, L.M. Grinsted14, M. Fazal15, M. Stuart16, J.F. Robertson9
1Lester and Sue Smith Breast Center, Baylor Clinic, Baylor College of Medicine, Houston, TX, USA, 2Oncology Department, Dnipropetrovsk State Medical Academy, Dnipropetrovsk, Ukraine, 3Department of Oncology, Leningrad Regional Oncology Centre, St-Petersburg, Russian Federation, 4Department of Oncology, Clinical Oncology Dispensary, Omsk, Russian Federation, 5Department of Oncology, Jewish General Hospital, Montreal, QC, Canada, 6City Clinical Oncology Dispensary, City Clinical Oncology Center, St. Petersburg, Russian Federation, 7Department of Chemotherapy, Lviv State Oncology Regional Treatment and Diagnostic Centre, Lviv, Ukraine, 8Technologico de Monterrey, Hospital San Jose, Monterrey, Mexico, 9Division of Medical Sciences and Graduate Entry Medicine, University of Nottingham, Derby, UK, 10Instituto Oncológico de Lima, Unidad de Investigación, Lima, Peru, 11Department of Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain, 12Shanghai Cancer Center, Fudan University, Shanghai, China, 13Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan, 14Global Medicines Development, AstraZeneca, Cambridge, UK, 15Global Medicines Development, AstraZeneca, Gaithersburg, MD, USA, 16Global Medicines Development, AstraZeneca, Macclesfield, UK
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
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.
Keywords: fulvestrant, anastrozole, breast cancer - metastatic, endocrine-naïve