Final analysis of the prospective WSG-AGO EC-Doc versus FEC phase III trial in intermediate-risk (pN1) early breast cancer: efficacy and predictive value of Ki67 expression |
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| Affiliation: | 1. Women‘s Clinic, Heinrich-Heine-University Duesseldorf, Duesseldorf;2. West German Study Group, Moenchengladbach;3. Breast Center Niederrhein, Ev. Bethesda Hospital, Moenchengladbach;4. Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen;5. Institute of Pathology, Hannover Medical School, Hannover;6. Institute of Pathology, University Clinics Erlangen, Erlangen;7. Trium Analysis Online GmbH, Munich;8. Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg;9. Department of Obstetrics and Gynecology, Staedtisches Klinikum, Frankfurt;10. Clinics Deggendorf Mammacenter Ostbayern, Deggendorf;11. Breast Center, St Josephs-Hospital, Wiesbaden;12. Women''s Clinic, Kreiskrankenhaus Boeblingen, Boeblingen;13. Department of Obstetrics and Gynecology, Ev. Hospital Oberhausen, Oberhausen;14. Breast Center, University Women''s Clinic Ulm, Ulm;15. Department of Gynecology and Oncology, Dr. Horst-Schmidt-Klinik GmbH, Wiesbaden;16. Deptartment of Gynecology and Obstetrics, Klinikum Rechts der Isar der Technischen Universität Muenchen (TUM), Munich;17. Breast Center, Women''s Clinic and CCCLMU of the University of Munich, Munich;18. Department of Gynecology, University Hospital Bonn, Bonn, Germany |
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| Abstract: | BackgroundTaxane-based adjuvant chemotherapy is standard in node-positive (N+) early breast cancer (BC). The magnitude of benefit in intermediate-risk N+ early BC is still unclear. WSG-AGO epiribicine and cyclophosphamide (EC)-Doc is a large trial evaluating modern taxane-based chemotherapy in patients with 1–3 positive lymph nodes (LNs) only.Patients and methodsA total of 2011 BC patients (18–65 years, pN1) were entered into a randomized phase III trial comparing 4 × E90C600 q3w followed by 4 × docetaxel100 q3w (n = 1008) with the current standard: 6 × F500E100C500 q3w (n = 828) or C600M40F600 d1, 8× q4w (n = 175). Primary end point was event-free survival (EFS); secondary end points were overall survival (OS), toxicity, translational research, and quality of life. Central tumor bank samples were evaluable in a representative collective (n = 772; 40%). Ki-67 was assessed centrally in hormone receptor-positive disease as a surrogate marker for the distinction of luminal A/B-like tumors.ResultsBaseline characteristics were well balanced between study arms in both main study and central tumor bank subset. At 59-month median follow-up, superior efficacy of EC-Doc [versus FEC (a combination of 5-fluorouracil, epirubicin, and cyclophosphamide)] was seen in EFS and OS: 5-year EFS: 89.8% versus 87.3% (P = 0.038); 5-year OS: 94.5% versus 92.8% (P = 0.034); both tests one-tailed. EC-Doc caused more toxicity. In hormone receptor-positive (HR)+ disease, only high-Ki-67 tumors (≥20%) derived significant benefit from taxane-based therapy: hazard ratio = 0.39 (95% CI 0.18–0.82) for EC-Doc versus FEC (test for interaction; P = 0.01).ConclusionEC-Doc significantly improved EFS and OS versus FEC in intermediate-risk BC (1–3 LNs) within all subgroups as defined by local pathology. In HR+ disease, patients with luminal A-like tumors may be potentially over-treated by taxane-based chemotherapy.Clinical Trial numberClinicalTrials.gov, NCT02115204. |
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