John F R Robertson1, Igor M Bondarenko2, Ekaterina Trishkina3, Mikhail Dvorkin4, Lawrence Panasci5, Alexey Manikhas6, Yaroslav Shparyk7, Servando Cardona-Huerta8, Kwok-Leung Cheung9, Manuel Jesus Philco-Salas10, Manuel Ruiz-Borrego11, Zhimin Shao12, Shinzaburo Noguchi13, Jacqui Rowbottom14, Mary Stuart14, Lynda M Grinsted15, Mehdi Fazal16, Matthew J Ellis17. 1. Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, UK. Electronic address: john.robertson@nottingham.ac.uk. 2. Oncology Department, Dnipropetrovsk State Medical Academy, Dnipropetrovsk, Ukraine. 3. Leningrad Regional Oncology Dispensary, St Petersburg, Russia. 4. Clinical Oncology Dispensary, Omsk, Russia. 5. Department of Oncology, Jewish General Hospital, Montreal, Canada. 6. City Clinical Oncology Dispensary, St Petersburg, Russia. 7. Lviv State Oncology Regional Treatment and Diagnostic Centre, Lviv, Ukraine. 8. Breast Cancer Center, Tecnológico de Monterrey, Monterrey, Mexico. 9. Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, UK. 10. Unidad de Investigación, Instituto Oncológico de Lima, Lima, Peru. 11. Hospital Universitario Virgen del Rocío, Seville, Spain. 12. Fudan University Shanghai Cancer Center, Shanghai, China. 13. Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. 14. AstraZeneca, Alderley Park, Macclesfield, UK. 15. AstraZeneca, Cambridge, UK. 16. AstraZeneca, Gaithersburg, MD, USA. 17. Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas, USA.
Abstract
BACKGROUND:Aromatase inhibitors are a standard of care for hormone receptor-positive locally advanced or metastatic breast cancer. We investigated whether the selective oestrogen receptor degrader fulvestrant could improve progression-free survival compared with anastrozole in postmenopausal patients who had not received previous endocrine therapy. METHODS: In this phase 3, randomised, double-blind trial, we recruited eligible patients with histologically confirmed oestrogen receptor-positive or progesterone receptor-positive, or both, locally advanced or metastatic breast cancer from 113 academic hospitals and community centres in 20 countries. Eligible patients were endocrine therapy-naive, with WHO performance status 0-2, and at least one measurable or non-measurable lesion. Patients were randomly assigned (1:1) to fulvestrant (500 mg intramuscular injection; on days 0, 14, 28, then every 28 days thereafter) or anastrozole (1 mg orally daily) using a computer-generated randomisation scheme. The primary endpoint was progression-free survival, determined by Response Evaluation Criteria in Solid Tumors version 1·1, intervention by surgery or radiotherapy because of disease deterioration, or death from any cause, assessed in the intention-to-treat population. Safety outcomes were assessed in all patients who received at least one dose of randomised treatment (including placebo). This trial is registered with ClinicalTrials.gov, number NCT01602380. FINDINGS:Between Oct 17, 2012, and July 11, 2014, 524 patients were enrolled to this study. Of these, 462 patients were randomised (230 to receivefulvestrant and 232 to receive anastrozole). Progression-free survival was significantly longer in the fulvestrant group than in the anastrozole group (hazard ratio [HR] 0·797, 95% CI 0·637-0·999, p=0·0486). Median progression-free survival was 16·6 months (95% CI 13·83-20·99) in the fulvestrant group versus 13·8 months (11·99-16·59) in the anastrozole group. The most common adverse events were arthralgia (38 [17%] in the fulvestrant group vs 24 [10%] in the anastrozole group) and hot flushes (26 [11%] in the fulvestrant group vs 24 [10%] in the anastrozole group). 16 (7%) of 228 patients in in the fulvestrant group and 11 (5%) of 232 patients in the anastrozole group discontinued because of adverse events. INTERPRETATION:Fulvestrant has superior efficacy and is a preferred treatment option for patients with hormone receptor-positive locally advanced or metastatic breast cancer who have not received previousendocrine therapy compared with a third-generation aromatase inhibitor, a standard of care for first-line treatment of these patients. FUNDING: AstraZeneca.
RCT Entities:
BACKGROUND: Aromatase inhibitors are a standard of care for hormone receptor-positive locally advanced or metastatic breast cancer. We investigated whether the selective oestrogen receptor degrader fulvestrant could improve progression-free survival compared with anastrozole in postmenopausal patients who had not received previous endocrine therapy. METHODS: In this phase 3, randomised, double-blind trial, we recruited eligible patients with histologically confirmed oestrogen receptor-positive or progesterone receptor-positive, or both, locally advanced or metastatic breast cancer from 113 academic hospitals and community centres in 20 countries. Eligible patients were endocrine therapy-naive, with WHO performance status 0-2, and at least one measurable or non-measurable lesion. Patients were randomly assigned (1:1) to fulvestrant (500 mg intramuscular injection; on days 0, 14, 28, then every 28 days thereafter) or anastrozole (1 mg orally daily) using a computer-generated randomisation scheme. The primary endpoint was progression-free survival, determined by Response Evaluation Criteria in Solid Tumors version 1·1, intervention by surgery or radiotherapy because of disease deterioration, or death from any cause, assessed in the intention-to-treat population. Safety outcomes were assessed in all patients who received at least one dose of randomised treatment (including placebo). This trial is registered with ClinicalTrials.gov, number NCT01602380. FINDINGS: Between Oct 17, 2012, and July 11, 2014, 524 patients were enrolled to this study. Of these, 462 patients were randomised (230 to receive fulvestrant and 232 to receive anastrozole). Progression-free survival was significantly longer in the fulvestrant group than in the anastrozole group (hazard ratio [HR] 0·797, 95% CI 0·637-0·999, p=0·0486). Median progression-free survival was 16·6 months (95% CI 13·83-20·99) in the fulvestrant group versus 13·8 months (11·99-16·59) in the anastrozole group. The most common adverse events were arthralgia (38 [17%] in the fulvestrant group vs 24 [10%] in the anastrozole group) and hot flushes (26 [11%] in the fulvestrant group vs 24 [10%] in the anastrozole group). 16 (7%) of 228 patients in in the fulvestrant group and 11 (5%) of 232 patients in the anastrozole group discontinued because of adverse events. INTERPRETATION:Fulvestrant has superior efficacy and is a preferred treatment option for patients with hormone receptor-positive locally advanced or metastatic breast cancer who have not received previous endocrine therapy compared with a third-generation aromatase inhibitor, a standard of care for first-line treatment of these patients. FUNDING: AstraZeneca.
Authors: F Cardoso; E Senkus; A Costa; E Papadopoulos; M Aapro; F André; N Harbeck; B Aguilar Lopez; C H Barrios; J Bergh; L Biganzoli; C B Boers-Doets; M J Cardoso; L A Carey; J Cortés; G Curigliano; V Diéras; N S El Saghir; A Eniu; L Fallowfield; P A Francis; K Gelmon; S R D Johnston; B Kaufman; S Koppikar; I E Krop; M Mayer; G Nakigudde; B V Offersen; S Ohno; O Pagani; S Paluch-Shimon; F Penault-Llorca; A Prat; H S Rugo; G W Sledge; D Spence; C Thomssen; D A Vorobiof; B Xu; L Norton; E P Winer Journal: Ann Oncol Date: 2018-08-01 Impact factor: 32.976
Authors: E Ciruelos; M Vidal; E Martínez de Dueñas; N Martínez-Jáñez; Y Fernández; J A García-Sáenz; L Murillo; F Carabantes; A Beliera; R Fonseca; J Gavilá Journal: Clin Transl Oncol Date: 2017-11-07 Impact factor: 3.405