Final Results of ABCSG-24, a Randomized Phase III Study Comparing Epirubicin, Docetaxel, and Capecitabine (EDC) to Epirubicin and Docetaxel (ED) as Neoadjuvant Treatment for Early Breast Cancer and Comparing ED/EDC + Trastuzumab (T) to ED/EDC as Neoadjuvant Treatment for Early HER-2 Positive Breast Cancer.

Abstract

Abstract Background: Since pathological complete responses (pCR) might be a surrogate for effective eradication of micrometastatic disease leading possibly to prolonged overall survival in primary breast cancer, neoadjuvant treatment of early breast cancer aims at achieving high rates of pCR.Methods: Primary aim of ABCSG-24 is to evaluate the influence of 6 cycles of EDC±T (experimental group) as compared to 6 cycles of ED±T (control group) on the rate of pCR at the time of surgery. 536 patients (pts) (268 pts/group, 5% dropout rate for 510 eligible pts, power=83%,p<0.05 (two-sided Chi²-test)) had to be accrued to detect a difference in pCR of 16% (ED±T) vs. 27% (EDC±T). 94 pts (47 pts/group,5% drop-out rate for 90 eligible pts, power=80%,p<0.05,two-sided Chi²-test) of the 536 pts must had a HER-2 positive (pos) tumor to detect a difference in pCR of 20% (ED/EDC)vs. 50% after ED/EDC+T.Between 11/2004 and 11/2008 536 pts with biopsy proven operable breast scheduled for neoadjuvant treatment (except T4d) +/- nodal involvement and without distant disease were stratified and randomized to receive either 6 x EDC every 21 days (day 1:E75 mg/m ² iv and D75 mg/m² iv,day 2:pegfilgrastim 6 mg sq, C: 2 x 1000 mg/m²/day days1-14 orally) or 6 cycles of identical ED without C. Pts with HER2pos tumors were also randomized to T 8mg/kg iv (day1) followed by 6mg/kg q 21 days or to no T.Results: 512 pts are eligible for toxicity and efficacy. In the intention to treat analysis there was no significant difference in the incidence of serious adverse events (EDC:26% vs. ED:21%,p=0,16) but significantly less patients completed the scheduled 6 cycles (EDC:75% vs. ED:97%,p<0.0001). After EDC significantly more pts had documented pCR (EDC:23,8% vs. ED:15,2%;p=0,036). In the HER2pos subgroup (eligible pts: n=90) there was a non-significant (p=0,369) difference in the rate of pCR after ED/EDC+T (40%) vs. ED/EDC (26,7%).Discussion: Neoadjuvant EDC in early breast cancer results in a significantly higher pCR rate than ED. ED/EDC + T leads to a non-significant higher rate of pCR than ED/EDC alone which might be due to a higher observed rate of pCR with ED/EDC alone than the expected. ED/EDC+/-T are feasible for outpatient use but C associated toxicity must be monitored closely and dose reduction rules must be observed. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1081.