Phase III randomised trial of doxorubicin (A) and docetaxel (D) versus A and cyclophosphamide (C) as primary medical therapy (PMT) in women with breast cancer

Abstract

521 Background: Use of PMT as pre-operative therapy for large primary, or locally advanced inoperable, breast cancer (BC)is increasing. Such regimens usually contain A,in combination with C (AC). D is among the most active single agents in metastatic BC and is increasingly used with A in advanced BC. Methods: Patients suitable for PMT (n=363) were randomised to receive up to 6 cycles of either (a) A (50mg/m2) and D (75mg/m2) i/v every 3 weeks, or (b) A (60mg/m2) and C (600mg/m2) i/v every 3 weeks. Patients with operable disease after completing chemotherapy had surgery followed by radiotherapy if indicated, and tamoxifen if ER+. We compared the response rates (clinical and pathological), relapse-free survival (RFS) after subsequent surgery, and overall survival (OS) of patients treated with AC and AD as PMT. Results: Patients with locally advanced inoperable (8%), inflammatory (15%) or large, operable (77%) primary BC, and with no evidence of metastatic disease, were randomised to AC (n=180) or AD (n=183). Clinical response rates (CR+PR) were 61% and 71% for AC and AD respectively (p=0.06). 7 patients treated with AC (4%) and 8 with AD (4%) received less than the planned 6 cycles of chemotherapy due to disease progression, with 14 patients (AC=8, AD=6) withdrawn early due to toxicity despite dose modifications. Pathological involvement of axillary LNs was present at surgery in 61% treated with AC and 66% with AD (p=0.28). Pathological CR rates for AC and AD were 24% and 21% respectively (p=0.61). No significant difference exists yet between the 2 groups for number of relapses. The median RFS and OS have not yet been reached with a median follow-up of 32 months. Conclusions: Both AC and AD are tolerated as PMT in primary BC. There is a trend to a superior clinical response rate with AD compared to AC, which does not reach statistical significance. There is no evidence of differences in the pathological CR rates or axillary LN involvement. In contrast to the positive results reported for sequential D following AC as PMT, our data do not suggest a benefit for simultaneous AD over AC. Updated analyses will be presented at conference. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis