5-year outcome for women randomised in a phase III trial comparing doxorubicin (A) and cyclophosphamide (C) with doxorubicin and docetaxel (D) as primary medical therapy of breast cancer: An Anglo-Celtic Cooperative Oncology Group Study

Abstract

540 Background: To compare the disease-free (DFS) and overall survival (OS), at a median follow up of 80 months, of women with primary or locally advanced breast cancer randomised to receive either doxorubicin and cyclophosphamide (AC) or doxorubicin and docetaxel (AD) as primary chemotherapy. Methods: Eligible patients (pts) with histologically-proven breast cancer with primary tumors > 3cm, inflammatory, or locally advanced disease, and no evidence of metastases, were randomised to receive a maximum of 6 cycles of either A (60 mg/m2) plus C (600 mg/m2) i/v every 3 weeks, or A (60 mg/m2) plus D (75 mg/m2) i/v every 3 weeks followed by surgery on completion of chemotherapy. Clinical and pathologic responses have previously been reported. Time to relapse, site of relapse, and all-cause mortality were recorded. The primary objective of this updated analysis was to determine the DFS and OS, which were assessed using stratified log-rank methods. Results: 363 pts were randomised to AC (n = 180) or AD (n = 183). Complete clinical and pathologic response rates were 17% and 24% for AC and 20% and 21% for AD (p = 0.42, 0.61, respectively). The number of pts with positive axillary lymph nodes at surgery was 61% (AC) and 66% (AD) (p = 0.28). The number of pts with pathologic complete response in the breast and negative axillary nodes at surgery was 16% for AC and 12% for AD. At a median follow-up of 80 months, there is no significant difference between AC and AD for DFS (p = 0.28), OS (p = 0.74), or for relapse site. The median DFS/OS were not estimable; the 25th percentile for DFS (OS) (75% of pts relapse free [alive]) was 20 (40) months and 25 (50) months for AC and AD, respectively. The 5-year DFS (95% CI) was 53% (47%-60%) for AC and 58% (52%-65%) for AD; 5-year OS (95% CI) was 67% (60%-74%) for AC and 71% (64%-78%) for AD. Site of relapse were local only (26%), distant only (56%), and both local and distant (18%). Distant relapse sites included bone (37%), liver (15%), lung (15%), pleura (7%), and soft tissue (2%). 92% of deaths were due to metastatic breast cancer. Conclusions: At a median follow-up of 80 months, our data do not suggest a DFS or OS benefit for simultaneous AD over AC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis