Abstract P3-14-08: A randomized phase II trial comparing docetaxel plus cyclophosphamide with epirubicin plus cyclophosphamide followed by docetaxel as neoadjuvant chemotherapy for hormone receptor-negative breast cancer. Kanagawa breast oncology group (KBOG) 1101 study

Abstract

Abstract Background: Taxane-based regimens have been developed and used widely to treat breast cancer. It has therefore become important to identify subgroups of patients in which anthracyclines are indispensable. Pathological response to neoadjuvant chemotherapy (NAC) predicts prognosis in hormone-negative subtypes. We therefore initiated a randomized phase II NAC study to compare a taxane with and without an anthracycline in these breast-cancer subtypes. Aim: To determine the safety and activity of six cycles of docetaxel and cyclophosphamide (TC6) compared with 5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel (FEC-D), and to examine the predictive factors for each regimen. Methods: Eligibility criteria were operable hormone-receptor-negative breast cancer, age younger than 75 years and ECOG PS0-1. According to HER2 status, patients were randomly assigned to TC (75/600 mg/m2) every 3 weeks X 6 or FEC (500/100/500 mg/m2) every 3 weeks X 3 followed by D (100 mg/m2) every 3 weeks X 3. The primary endpoint was the rate of pathological complete response (pCR; grade 3). Triple-negative (TN) breast cancer was subdivided by cytokeratin 5/6 and epidermal growth factor receptor into basal- and non-basal subtypes. Secondary endpoints were safety, breast-conserving surgery, disease-free survival, overall survival, and predictive factors: Ki-67, p53, aldehyde dehydrogenase (ALDH) 1 and topoisomerase 2A by both immunohistochemistry and fluorescence in situ hybridization for each regimen. Results: Ninety-seven of 103 patients were analyzed successfully (50 for FEC-D and 47 for TC6). Significantly more severe adverse events (grade 2) were observed in FEC-D-treated patients (poor appetite, nausea and vomiting: p = 0.001; febrile neutropenia: p = 0.016). The pCR rate tended to be higher in FEC-D-treated patients compared with TC6-treated patients (pCR: 36.0 vs. 25.5%, n.s.). FEC-D treatment was significantly more effective than TC6 in basal-type (p = 0.033) but not in non-basal and HER2 subtypes. ALDH1 was associated with resistance to both regimens (FEC-D: p = 0.047, TC6: p = 0.085) Conclusions: TC6 was safer, but not more effective than FEC-D. TC6 was significantly less active than FEC-D in basal subtype, and equivalent to FEC-D in HER2 and non-basal subtypes. Concurrent use of trastuzumab with TC could thus represent a reasonable option for NAC in HER2-subtype patients. ALDH1 could provide a marker for novel strategies such as stem cell-based therapies for breast cancer. Analyses on pathological factors in surgical specimens after NAC will be presented at the meeting. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-08.