Abstract P1-14-02: Preoperative docetaxel (T) with or without capecitabine (X) following epirubicin, 5-fluorouracil and cyclophosphamide (FEC) in patients with operable breast cancer (OOTR N003): Results of comparative study and predictive marker analysis
Authors: Toi M , Ohno S , Sato N , Masuda N , Sasano H , Takahashi F , Bando H , Iwata H , Morimoto T , Kamigaki S , Nakayama T , Murakami S , Nakamura S , Kuroi K , Aogi K , Kashiwaba M , Yamashita H , Hisamatsu K , Ito Y , Yamamoto Y , Ueno T , Fakhrejahani E , Yoshida N , Chow LWC 
Published: August 2014

Abstract
Objective: This preoperative study aimed to evaluate the efficacy of 4 cycles of TX compared with 4 cycles of T, following 4 cycles of FEC in operable breast cancer patients.
Methods: Women with operable breast cancer (T1C-3N0M0/T1-3N1M0) were randomly assigned to receive either T (75 mg/m2, q3) plus X (825 mg/m2 bid, days 1 to 14) or T alone (75 mg/m2, q3) after completion of FEC (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2, q3). Patients who had disease progression on FEC were excluded from randomization. The primary endpoint was pathological complete response (pCR). Predictive factor analysis was conducted using clinicopathological markers such as hormone receptors, Ki67 labeling index (Ki67LI) and thymidine phosphorylase (TP).
Results: From November 2005 to October 2009, 504 patients were enrolled and 239 and 238 patients were assigned to TX and T group, respectively (median age 49 years, median tumor size 3.5 cm and node positive rate 56%). Treatment discontinuation was observed in 22% of TX group and 5% in T group (p &lt; 0.0001). The major reasons for discontinuation were toxicity, refusal/ consent withdrawal and several others. No significant difference in pCR rate was shown between the two groups (TX 23% and T 24%, p = 0.748). Neither clinical response nor surgical outcome differed between TX and T. The pCR rate in patients who had therapy discontinuation or dose-reduction on TX was 23%, whereas pCR rate in those on T was 11%. A subpopulation treatment effect pattern plots method indicated a trend that TX may improve the pCR rate in patients having a middle range of pretreatment Ki67LI, such as 10%–20%. In the median follow-up time of 3.7 years, disease-free survival (DFS) was not different between TX and T (3-year DFS: 92% in TX and 91% in T; hazard ratio 0.907, 95%CI 0.528–1.557, p = 0.723). The frequency of major grade 3 or greater adverse events of TX and T were leukopenia, 36% and 34%, febrile neutropenia 8% and 5%, and hand-foot syndrome 15% and 2%, respectively.
According to the analysis for evaluating predictive values of biomarkers, a multivariate logistic regression analysis showed that HER2 (+/−: odds ratio 4.107, p &lt; 0.0001), Ki67LI (continuous variables: 1.029, p = 0.003), hormone receptor status (+/−: 0.457, p = 0.009), stroma TP status (0.523, p = 0.02) and grade (1/3: 0.387, 2/3: 0.532, p = 0.047) had statistical significant values for predicting pCR. A multiple Cox model in landmark analysis showed that tumor size (p &lt; 0.0001), cancer cell TP status (p = 0.005), pCR and posttreatment Ki67LI (p = 0.016), and age (p = 0.049) were associated with DFS significantly.
Conclusions: Addition of X to T showed no superiority to T alone following FEC in neoadjuvant treatment of these patients with operable breast cancer. Treatment discontinuation rate was significantly higher in TX than T group, however the pCR rate in patients in TX group who required treatment discontinuation or dose-reduction was similar to that in patients who completed as scheduled, which was different from T group. Determination of pre-/ post-treatment Ki67LI looks useful for predicting pCR and DFS.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-02.