Comparison of an AC-taxane versus AC-free regimen and paclitaxel versus docetaxel in patients with lymph node-positive breast cancer: Final results of the National Surgical Adjuvant Study of Breast Cancer 02 trial, a randomized comparative phase 3 study

Abstract

Background: In postoperative patients with breast cancer, the combination of an anthracycline and cyclophosphamide (AC) followed by a taxane is a standard regimen. In the current study, the authors examined whether AC could be safely omitted, and compared the effectiveness of paclitaxel versus docetaxel.

Methods: Female postoperative patients with axillary lymph node-positive breast cancer were eligible for enrollment in this phase 3, open-label, randomized controlled trial at 84 centers in Japan. Patients were randomized to 4 cycles of doxorubicin at a dose of 60 mg/m² and cyclophosphamide at a dose of 600 mg/m² (AC) followed by 4 cycles of paclitaxel at a dose of 175 mg/m² (ACpT) or AC followed by 4 cycles of docetaxel at a dose of 75 mg/m² (ACdT), or 8 cycles of paclitaxel (PTx) or docetaxel (DTx) every 3 weeks. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival adverse events. The authors adopted a 2 × 2 factorial design to examine the AC containing-regimens (ACpT and ACdT) versus the AC free-regimens (PTx and DTx), and the paclitaxel-containing regimens (ACpT and PTx) versus the docetaxel-containing regimens (ACdT and DTx).

Results: Of 1060 patients, 1049 were treated and included in the intention-to-treat population. The DFS results did not demonstrate noninferiority between the AC-containing and the AC-free regimens (hazard ratio [HR], 1.19; 95% confidence interval [95% CI], 0.982-1.448 [P_{noninferiority} = .30]). Better outcomes were noted in patients treated with the docetaxel-containing regimens compared with the paclitaxel-containing regimens with respect to DFS (HR, 0.72; 95% CI, 0.589-0.875 [P = .0008]) and overall survival (HR, 0.75; 95% CI, 0.574-0.980 [P = .035]). Neutropenia, nausea, and vomiting were found to occur more often in the AC-containing arms, whereas the incidence of edema was greater in the docetaxel-containing treatment arms.

Conclusions: Noninferiority in DFS was not demonstrated between the AC-containing and AC-free regimens. Compared with a similar regimen of paclitaxel, docetaxel appeared to increase the DFS. Cancer 2017;123:759-68. © 2016 American Cancer Society.

Keywords: adjuvant therapy; docetaxel; doxorubicin and cyclophosphamide (AC)-taxane; paclitaxel; randomized phase 3.