gms | German Medical Science

Background: Sequential AC-DOC is more effective than dose-dense ADOC as preoperative treatment regarding pathologic complete response in patients with breast cancer. Whether this advantage translates into improved survival rates needs to be shown.

Methods: 913 women with primary operable breast cancer (T2‑3, N0‑2, M0) were randomized either to receive doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 every 14 days for four cycles with G-CSF support (ADOC; n=455) or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 21 days followed by docetaxel 100 mg/m2 every 21 days for four cycles each (AC‑DOC; n=458). The primary endpoint was the rate of pathologic complete response (pCR) in the breast and axillary nodes (von Minckwitz et al., J Clin Oncol 2005).

Results: After 5 years of follow-up in the ADoc group 112 pts relapsed or died whereas in the AC-Doc group 113 events have been observed giving a five-year event-free survival rate of 65.0% in the ADOC- and 66.1% in the AC-DOC group (log-rank: P=0.66). 57 patients have died in the ADoc group and 48 in the AC-Doc group. The five-year overall survival rates are estimated as 81.0% in the ADOC group and 84.8% in the AC-DOC arm (log rank: P=0.24).

Conclusion: Although the first evaluation of the GEPARDUO trial showed an advantage of sequential AC-DOC as preoperative treatment at inducing pathologic complete response for patients with operable breast cancer, this first analysis of event free and overall survival offers no statistically significant difference of AC-DOC over the dose-dense ADoc.

However, these results are concordant with the results by the NSABP-B27 when the advantage of inducing a higher pCR rate by the AC-Doc arm could only be transformed into a trend for a survival benefit.

We hypothesize that the pCR rate magnifies differences in treatment effects which can otherwise only be demonstrated in large scale trials with a long term follow-up.