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.
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.



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.



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).



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.



ClinicalTrials.gov, NCT02115204.
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.
U
U
Nitz
West German Study Group, Moenchengladbach Breast Center Niederrhein, Ev. Bethesda Hospital, Moenchengladbach.
O
O
Gluz
Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen.
J
J
Huober
Institute of Pathology, Hannover Medical School, Hannover.
H H
HH
Kreipe
West German Study Group, Moenchengladbach.
R E
RE
Kates
Institute of Pathology, University Clinics Erlangen, Erlangen.
A
A
Hartmann
Institute of Pathology, University Clinics Erlangen, Erlangen.
R
R
Erber
Z
Z
Moustafa
Trium Analysis Online GmbH, Munich.
M
M
Scholz
Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg.
B
B
Lisboa
Women's Clinic, Heinrich-Heine-University Duesseldorf, Duesseldorf.
S
S
Mohrmann
Department of Obstetrics and Gynecology, Staedtisches Klinikum, Frankfurt.
V
V
Möbus
Clinics Deggendorf Mammacenter Ostbayern, Deggendorf.
D
D
Augustin
Breast Center, St Josephs-Hospital, Wiesbaden.
G
G
Hoffmann
Women's Clinic, Kreiskrankenhaus Boeblingen, Boeblingen.
E
E
Weiss
Department of Obstetrics and Gynecology, Ev. Hospital Oberhausen, Oberhausen.
S
S
Böhmer
Breast Center, University Women's Clinic Ulm, Ulm.
R
R
Kreienberg
Department of Gynecology and Oncology, Dr. Horst-Schmidt-Klinik GmbH, Wiesbaden.
A
A
Du Bois
Deptartment of Gynecology and Obstetrics, Klinikum Rechts der Isar der Technischen Universität Muenchen (TUM), Munich.
D
D
Sattler
Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg.
C
C
Thomssen
Deptartment of Gynecology and Obstetrics, Klinikum Rechts der Isar der Technischen Universität Muenchen (TUM), Munich.
M
M
Kiechle
Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg.
F
F
Jänicke
Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen.
D
D
Wallwiener
West German Study Group, Moenchengladbach Breast Center, Women's Clinic and CCCLMU of the University of Munich, Munich.
N
N
Harbeck
Department of Gynecology, University Hospital Bonn, Bonn, Germany.
W
W
Kuhn
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil
adjuvant chemotherapy; luminal A/B-like subtypes; node-positive breast cancer; overtreatment