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

被引：38

作者：

Nitz, U. ^{[1
,2
,3
]}

Gluz, O. ^{[2
,3
]}

Huober, J. ^{[4
]}

Kreipe, H. H. ^{[5
]}

Kates, R. E. ^{[2
]}

Hartmann, A. ^{[6
]}

Erber, R. ^{[6
]}

Scholz, M. ^{[7
]}

Lisboa, B. ^{[8
]}

Mohrmann, S. ^{[1
]}

Moebus, V. ^{[9
]}

Augustin, D. ^{[10
]}

Hoffmann, G. ^{[11
]}

Weiss, E. ^{[12
]}

Boehmer, S. ^{[13
]}

Kreienberg, R. ^{[14
]}

Du Bois, A. ^{[15
]}

Sattler, D. ^{[16
]}

Thomssen, C. ^{[8
]}

Kiechle, M. ^{[16
]}

Jaenicke, F. ^{[8
]}

Wallwiener, D. ^{[4
]}

Harbeck, N. ^{[2
,17
,18
]}

Kuhn, W. ^{[19
]}

机构：

[1] Univ Duesseldorf, Womens Clin, Dusseldorf, Germany

[2] West German Study Grp, D-41061 Monchengladbach, Germany

[3] Ev Bethesda Hosp, Breast Ctr Niederrhein, Monchengladbach, Germany

[4] Univ Tubingen, Dept Obstet & Gynecol, Tubingen, Germany

[5] Hannover Med Sch, Inst Pathol, Hannover, Germany

[6] Univ Clin Erlangen, Inst Pathol, Erlangen, Germany

[7] Trium Anal Online GmbH, Munich, Germany

[8] Univ Med Ctr Hamburg Eppendorf, Dept Gynecol, Hamburg, Germany

[9] Staedt Klinikum, Dept Obstet & Gynecol, Frankfurt, Germany

[10] Mammactr Ostbayern, Clin Deggendorf, Deggendorf, Germany

[11] St Josephs Hosp, Breast Ctr, Wiesbaden, Germany

[12] Kreiskrankenhaus Boeblingen, Womens Clin, Boblingen, Germany

[13] Ev Hosp Oberhausen, Dept Obstet & Gynecol, Oberhausen, Germany

[14] Univ Womens Clin Ulm, Breast Ctr, Ulm, Germany

[15] Dr Horst Schmidt Klin GmbH, Dept Gynecol & Oncol, Wiesbaden, Germany

[16] Tech Univ Munich, Klinikum Rechts Isar, Dept Gynecol & Obstet, D-80290 Munich, Germany

[17] Univ Munich, Womens Clin, Breast Ctr, Munich, Germany

[18] Univ Munich, CCCLMU, Munich, Germany

[19] Univ Hosp Bonn, Dept Gynecol, Bonn, Germany

来源：

ANNALS OF ONCOLOGY | 2014年 / 25卷 / 08期

关键词：

adjuvant chemotherapy; node-positive breast cancer; luminal A/B-like subtypes; overtreatment; BCIRG; 001; TRIAL; ADJUVANT TREATMENT; SEQUENTIAL DOCETAXEL; RANDOMIZED-TRIAL; CHEMOTHERAPY; DOXORUBICIN; PACLITAXEL; WOMEN; REGIMENS;

D O I：

10.1093/annonc/mdu186

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 x E90C600 q3w followed by 4 x docetaxel(100) q3w (n = 1008) with the current standard: 6 x F500E100C500 q3w (n = 828) or C600M40F600 d1, 8x 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.

引用

页码：1551 / 1557

页数：7