PD07-02: Docetaxel Is Superior to Paclitaxel Given Every Three Weeks in Post Operative Patients with Node-Positive Breast Cancer: Results of the Final Analyses of the NSAS-BC (National Surgical Adjuvant Study of Breast Cancer) 02 Trial from Japan.

Abstract

Abstract Background: Four cycles of doxorubicin plus cyclophosphamide (4-AC) followed by four cycles of a taxane is widely used for postoperative chemotherapy in breast cancer (BC). Concern about relatively rare, but life-threatening toxicity of anthracyclines such as heart failure and secondary leukemia has promoted research to seek anthracycline-free regimens. Since 1990's when taxanes were introduced, docetaxel (DTX) is used interchangeably with paclitaxel (PTX) for the treatment of BC, but they may differ more than initially anticipated. We conducted this trial to test two hypotheses: (1) Eight cycles of a taxane is not inferior to 4-AC followed by four cycles of a taxane; (2) one taxane is superior to the other. Methods: Eligibility included a diagnosis of clinical stage I-IIIA and axillary node-positive BC, an age younger than 71 years and with performance status of 0 to 1. Patients were randomly assigned to receive either one of the following regimens;ACP: 4-AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 q3w x 4) followed by 4-PTX (175 mg/m2 q3w x 4)ACD: 4-AC followed by 4-DTX (75 mg/m2 q3w x 4)8-PTX: PTX (175 mg/m2 q3w x 8)8-DTX: DTX (75 mg/m2 q3w x 8) Comparisons included PTX vs. DTX (ACP + 8-PTX vs. ACD + 8-DTX) and +AC vs. -AC (ACP + ACD vs. 8-PTX + 8-DTX). The primary endpoint was disease-free survival (DFS), and the secondary endpoints include overall survival (OS). The trial was powered to prove the non-inferiority of +AC to -AC (threshold hazard ratio 1.32) in terms of DFS. DFS was also compared between PTX and DTX to determine any superiority. Results: A total of 1,060 eligible patients were accrued at 84 centers between December 2001 and April 2006. There were 348 DFS events and 166 deaths after a median followup of 72.2 months. DTX was superior to PTX in terms of both DFS (Hazard ratio(HR) 0.76; 95% Confidence Interval(CI) 0.62−0.95, p=0.012) and OS (HR 0.72;95%CI 0.53−0.97, p=0.033). -AC was not inferior to +AC with respect to DFS (HR: 1.21, 90% CI 1.01−1.44). Among the four arms, 8-PTX alone resulted in poorer DFS (compared with ACP, HR 1.42 95%CI 1.07−1.89). Nausea and vomiting were more frequent with +AC than -AC. Edema and febrile neutropenia were more frequent with DTX than PTX. The incidence of sensory neuropathy was higher with PTX than DTX and it lasted for more than one year of the end of PTX treatment. Conclusions: When AC, PTX and DTX were given every three weeks, both DFS and OS were better in the arms including DTX than in those including PTX. AC followed by a taxane can be replaced by 8-DTX. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD07-02.