TY - JOUR
T1 - Randomized trial of preoperative docetaxel with or without capecitabine after 4 cycles of 5-fluorouracil-epirubicin-cyclophosphamide (FEC) in early-stage breast cancer
T2 - Exploratory analyses identify Ki67 as a predictive biomarker for response to neoadjuvant chemotherapy
AU - Ohno, S.
AU - Chow, L. W.C.
AU - Sato, N.
AU - Masuda, N.
AU - Sasano, H.
AU - Takahashi, F.
AU - Bando, H.
AU - Iwata, H.
AU - Morimoto, T.
AU - Kamigaki, S.
AU - Nakayama, T.
AU - Nakamura, S.
AU - Kuroi, K.
AU - Aogi, K.
AU - Kashiwaba, M.
AU - Yamashita, H.
AU - Hisamatsu, K.
AU - Ito, Y.
AU - Yamamoto, Y.
AU - Ueno, T.
AU - Fakhrejahani, E.
AU - Yoshida, N.
AU - Toi, M.
N1 - Funding Information:
Acknowledgments This study was made possible by the generous support and supply of knowledge by Product Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd. and Sanofi K.K., Japan. This work was supported by an unconditional grant from Sanofi K.K., Japan.
PY - 2013/11
Y1 - 2013/11
N2 - This randomized, multicenter study compared the efficacy of docetaxel with or without capecitabine following fluorouracil/epirubicin/cyclophosphamide (FEC) therapy in operable breast cancer and investigated the role of Ki67 as a predictive biomarker. Patients were randomized to 4 cycles of docetaxel/capecitabine (docetaxel: 75 mg/m2 on day 1; capecitabine: 1,650 mg/m2 on days 1-14 every 3 weeks) or docetaxel alone (75 mg/m2 on day 1 every 3 weeks) after completion of 4 cycles of FEC (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 every 3 weeks). The primary endpoint was the pathological complete response (pCR) rate. Predictive factor analysis was conducted using clinicopathological markers, including hormone receptors and Ki67 labeling index (Ki67LI). A total of 477 patients were randomized; the overall response in the docetaxel/capecitabine and docetaxel groups was 88.3 and 87.4 %, respectively. There were no significant differences in the pCR rate (docetaxel/capecitabine: 23 %; docetaxel: 24 %; p = 0.748), disease-free survival, or overall survival. However, patients with mid-range Ki67LI (10-20 %) showed a trend towards improved pCR rate with docetaxel/capecitabine compared to docetaxel alone. Furthermore, multivariate logistic regression analysis showed pre-treatment Ki67LI (odds ratio 1.031; 95 % CI 1.014-1.048; p = 0.0004) to be a significant predictor of pCR in this neoadjuvant treatment setting. Docetaxel/capecitabine (after 4 cycles of FEC) did not generate significant improvement in pCR compared to docetaxel alone. However, exploratory analyses suggested that assessment of pre-treatment Ki67LI may be a useful tool in the identification of responders to preoperative docetaxel/capecitabine in early-stage breast cancer.
AB - This randomized, multicenter study compared the efficacy of docetaxel with or without capecitabine following fluorouracil/epirubicin/cyclophosphamide (FEC) therapy in operable breast cancer and investigated the role of Ki67 as a predictive biomarker. Patients were randomized to 4 cycles of docetaxel/capecitabine (docetaxel: 75 mg/m2 on day 1; capecitabine: 1,650 mg/m2 on days 1-14 every 3 weeks) or docetaxel alone (75 mg/m2 on day 1 every 3 weeks) after completion of 4 cycles of FEC (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 every 3 weeks). The primary endpoint was the pathological complete response (pCR) rate. Predictive factor analysis was conducted using clinicopathological markers, including hormone receptors and Ki67 labeling index (Ki67LI). A total of 477 patients were randomized; the overall response in the docetaxel/capecitabine and docetaxel groups was 88.3 and 87.4 %, respectively. There were no significant differences in the pCR rate (docetaxel/capecitabine: 23 %; docetaxel: 24 %; p = 0.748), disease-free survival, or overall survival. However, patients with mid-range Ki67LI (10-20 %) showed a trend towards improved pCR rate with docetaxel/capecitabine compared to docetaxel alone. Furthermore, multivariate logistic regression analysis showed pre-treatment Ki67LI (odds ratio 1.031; 95 % CI 1.014-1.048; p = 0.0004) to be a significant predictor of pCR in this neoadjuvant treatment setting. Docetaxel/capecitabine (after 4 cycles of FEC) did not generate significant improvement in pCR compared to docetaxel alone. However, exploratory analyses suggested that assessment of pre-treatment Ki67LI may be a useful tool in the identification of responders to preoperative docetaxel/capecitabine in early-stage breast cancer.
KW - Breast cancer
KW - Capecitabine
KW - Docetaxel
KW - Ki67
KW - Neoadjuvant chemotherapy
KW - Pathological complete response
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UR - http://www.scopus.com/inward/citedby.url?scp=84888246639&partnerID=8YFLogxK
U2 - 10.1007/s10549-013-2691-y
DO - 10.1007/s10549-013-2691-y
M3 - Article
C2 - 24122389
AN - SCOPUS:84888246639
VL - 142
SP - 69
EP - 80
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 1
ER -
