U Nitz1, O Gluz2, J Huober3, H H Kreipe4, R E Kates5, A Hartmann6, R Erber6, Z Moustafa, M Scholz7, B Lisboa8, S Mohrmann9, V Möbus10, D Augustin11, G Hoffmann12, E Weiss13, S Böhmer14, R Kreienberg15, A Du Bois16, D Sattler17, C Thomssen8, M Kiechle17, F Jänicke8, D Wallwiener3, N Harbeck18, W Kuhn19. 1. Women's Clinic, Heinrich-Heine-University Duesseldorf, Duesseldorf West German Study Group, Moenchengladbach Breast Center Niederrhein, Ev. Bethesda Hospital, Moenchengladbach ulrike.nitz@wsg-online.com wsg@wsg-online.com. 2. West German Study Group, Moenchengladbach Breast Center Niederrhein, Ev. Bethesda Hospital, Moenchengladbach. 3. Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen. 4. Institute of Pathology, Hannover Medical School, Hannover. 5. West German Study Group, Moenchengladbach. 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. Women's Clinic, Heinrich-Heine-University Duesseldorf, Duesseldorf. 10. Department of Obstetrics and Gynecology, Staedtisches Klinikum, Frankfurt. 11. Clinics Deggendorf Mammacenter Ostbayern, Deggendorf. 12. Breast Center, St Josephs-Hospital, Wiesbaden. 13. Women's Clinic, Kreiskrankenhaus Boeblingen, Boeblingen. 14. Department of Obstetrics and Gynecology, Ev. Hospital Oberhausen, Oberhausen. 15. Breast Center, University Women's Clinic Ulm, Ulm. 16. Department of Gynecology and Oncology, Dr. Horst-Schmidt-Klinik GmbH, Wiesbaden. 17. Deptartment of Gynecology and Obstetrics, Klinikum Rechts der Isar der Technischen Universität Muenchen (TUM), Munich. 18. West German Study Group, Moenchengladbach Breast Center, Women's Clinic and CCCLMU of the University of Munich, Munich. 19. Department of Gynecology, University Hospital Bonn, Bonn, Germany.
Abstract
BACKGROUND:Taxane-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 METHODS: A total of 2011 BC patients (18-65 years, pN1) were entered into a randomized phase III trial comparing 4 × E90C600 q3w followed by 4 × docetaxel 100 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. RESULTS: Baseline 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). CONCLUSION:EC-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 NUMBER: ClinicalTrials.gov, NCT02115204.
RCT Entities:
BACKGROUND:Taxane-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 METHODS: A total of 2011 BC patients (18-65 years, pN1) were entered into a randomized phase III trial comparing 4 × E90C600 q3w followed by 4 × docetaxel 100 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. RESULTS: Baseline 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). CONCLUSION:EC-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 NUMBER: ClinicalTrials.gov, NCT02115204.
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