Abstract
Purpose
GEICAM/2006–10 compared anastrozole (A) versus fulvestrant plus anastrozole (A + F) to test the hypothesis of whether a complete oestrogen blockade is superior to aromatase inhibitors alone in breast cancer patients receiving hormone adjuvant therapy.
Methods
Multicenter, open label, phase III study. HR+/HER2− EBC postmenopausal patients were randomized 1:1 to adjuvant A (5 years [year]) or A + F (A plus F 250 mg/4 weeks for 3 year followed by 2 year of A). Stratification factors: prior chemotherapy (yes/no); number of positive lymph nodes (0/1–3/≥ 4); HR status (both positive/one positive) and site. Primary objective: disease-free survival (DFS). Planned sample size: 2852 patients.
Results
The study has an early stop due to the financer decision with 870 patients (437 randomized to A and 433 to A + F). Patient characteristics were well balanced. After a median follow-up of 6.24y and 111 DFS events (62 in A and 49 in A + F) the Hazard Ratio for DFS (combination vs. anastrozole) was 0.84 (95% CI 0.58–1.22; p = 0.352). The proportion of patients disease-free in arms A and A + F at 5 year and 7 year were 90.8% versus 91% and 83.6% versus 86.7%, respectively. Most relevant G2-4 toxicities (≥ 5% in either arm) with A versus A + F were joint pain (14.7%; 13.7%), fatigue (2.5%; 7.2%), bone pain (3%; 6.5%), hot flushes (3.5%; 5%) and muscle pain (2.8%; 5.1%).
Conclusions
The GEICAM/2006–10 study did not show a statistically significant increase in DFS by adding adjuvant F to A, though no firm conclusions can be drawn because of the limited sample size due to the early stop of the trial. ClinicalTrials.gov: NCT00543127.
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Acknowledgements
We thank all the investigators involved in the GEICAM/2006–10 study (M.A. Seguí, F. Ayala, J. de la Haba, P. Martínez, S. González, A. Lahuerta, J.C. Toral, E. Martínez de Dueñas, J. Florián, M.J. Godes, C. Llorca, I. Blancas, C. Jara, S. Morales, A. Arcusa, A. Martínez, E. Vicente, A. de Juan, M. Rodríguez, M. García, P. García, J.L. Bayo, V. Carañana, J. Casinello, L. Jolis, M. Gil, C. Cañabate, A. Oltra, J. Ramírez, M. Lomas, A. Barnadas, M. Sureda, F. Carabantes, I. Moreno, A.L. Moreno). We also thank all of the participating patients and local research staff as well as the GEICAM staff.
Funding
The study was sponsored by GEICAM Spanish Breast Cancer Group. AstraZeneca Farmaceutica Spain provided fulvestrant and funding for the trial.
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B Bermejo her institution has received research funding from AstraZeneca, Merck, Roche Pharma AG, Boehringer Ingelheim, Novartis and Roche outside the current trial. M. Ramos has participated in advisory boards of AstraZeneca, Roche, Novartis and Pfizer and received speaker honoraria from AstraZeneca, Roche, Novartis and Pfizer. J. Cruz has participated in advisory boards of AstraZeneca, Roche, Novartis, Pharmamar, Eisai, Lilly, Celgene, Astellas, Amgen, Glaxo, and Pfizer and received speaker honoraria from Glaxo, AstraZeneca, Roche, Novartis, Pharmamar, Eisai, Lilly, Celgene, Astellas, Amgen, and Pfizer. J.M. Baena-Cañada has participated in advisory boards of AstraZeneca, Roche, Novartis, Amgen, Bristol, Eisay, Celgene and Pfizer and received speaker honoraria from Roche and Ferrer. His institution has received research funding from AstraZeneca. B. Cirauqui has received speaker honoraria and funding for some independent medical education activities from Astra Zeneca outside de current trial. A Rodríguez-Lescure has participated in advisory boards of Roche, Novartis, MSD and Pfizer and has received speaker honoraria from AstraZeneca, Roche, Novartis, Kern Pharma, Amgen, and Pfizer; his institution has received research funding from Novartis, Pfizer, Lilly and Roche outside the current trial. E. Alba has participated in advisory boards of Roche, Pfizer, Novartis and Lilly, his institution has received funding from Roche and Sysmex. N. Martínez Jañez has participated in advisory boards of AstraZeneca, Roche, Novartis, Celgene, Eisai, and Pfizer and received speaker honoraria from Roche, Novartis, Eisai and Pfizer. M. Muñoz: has participated in advisory boards of AstraZeneca, Merck and Novartis and expert opinion of Roche. She has received scientific meetings travel expenses from AstraZeneca and Roche. I. Álvarez López has participated in consultant or advisory boards of AstraZeneca, Pfizer, Palex, Roche, Novartis and received speaker honoraria from AstraZeneca, Pfizer, Roche, Eisai, received scientific meetings travel expenses from Pfizer and Roche. Her institution has received research funding from AstraZeneca, Pfizer, Roche, Novartis outside the current trial. A. Antón: has participated in consultant or advisory boards of Bayer. Him institution has received research funding from Roche outside the current trial. E. Carrasco´s immediate family member has participated in advisory boards of Pfizer and received speaker honoraria form Pfizer and his institution has received research funding from Pfizer. M. Martin has participated in advisory boards of AstraZeneca, Roche, Novartis, Pharmamar, Amgen, and Pfizer and received speaker honoraria from Glaxo, AstraZeneca, Roche, Novartis, Amgen, and Pfizer; his institution has received research funding from Novartis and Roche outside the current trial. E. Sevillano has received speaker honorary from Roche, Eisai, MSD and Ipsen. GEICAM has received funding from AstraZeneca for some independent medical education activities and research projects performed by the Group in which all authors collaborated. Rest of authors declare no conflict of interest.
Ethical approval
The study was performed in accordance with the Declaration of Helsinki, approved by the institutions’ ethical committees and health authorities in Spain, and registered at EUDRACT (2007-003417-14) and ClinicalTrials.gov (NCT00543127). Written informed consent was obtained from all patients before performing any protocol specific procedure.
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The members of GEICAM participant investigators are listed in “Acknowledgement” section.
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Ruíz-Borrego, M., Guerrero-Zotano, A., Bermejo, B. et al. Phase III evaluating the addition of fulvestrant (F) to anastrozole (A) as adjuvant therapy in postmenopausal women with hormone receptor-positive HER2-negative (HR+/HER2−) early breast cancer (EBC): results from the GEICAM/2006–10 study. Breast Cancer Res Treat 177, 115–125 (2019). https://doi.org/10.1007/s10549-019-05296-8
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DOI: https://doi.org/10.1007/s10549-019-05296-8