Phase III randomized trial of primary chemotherapy with doxorubicin/cyclophosphamide (AC) vs docetaxel/capecitabine (TX) for stage II/III breast cancer (BC): Interim analysis

Abstract

607 Background: Recent data suggested docetaxel (T) when added preoperatively to enhance tumor response following AC, significantly improved pathologic tumor response and clinical outcomes. In metastatic BC, TX resulted in higher RR, TTP and OS compared with T alone. Therefore, a phase III study was designed to compare efficacy and toxicity of AC vs TX as primary chemotherapy for stage II/III BC. Methods: Patients (pts) with stage II/III BC without prior hormonal, chemo-, radiation therapy, or surgery (op) other than biopsy were eligible. Pts must have positive axillary LN by PET or sono guided diagnosis, adequate organ and hematologic profiles and good PS (ECOG 0/1). Randomization to receive preoperative AC x 4 (A 60mg/m2 i.v. d1/C 600 mg/m2 i.v. d1 q 3 wk) vs TX x 4 (T 75 mg/m2 i.v. d1/X 1,000mg/m2 p.o. BID d1–14 q 3 wk) was based on stage, ER status, and age. Postoperatively, therapy crosses over to the other arm. Further radiation ± tamoxifen is given. Assessment for clinical response was assisted by 3 serial sono results at baseline, after 2nd and 4th cycles. Results: Total 78 pts were enrolled from 8/02 to 11/03. Age (range 21–66yrs), stage II (56%), ER (54%), HER2 3+ (28%) were well balanced in 2 arms. Thus far, 32 pts in AC /33 in TX completed op. Clinically, 1 CR, 23 PR, 1 MR, 4 SD, 3 PD in AC arm vs 1 CR, 28 PR, 3 MR, 1 SD, 0 PD in TX arm were observed (p=0.03). pCR of primary tumor was 6.3%, AC vs 15.2%, TX (p=0.43), and in LN, 29% vs 27%. Relative dose intensity (%) were 97/96 in AC vs 95/90 in TX. Severe adverse events were G3/4 neutropenia (94 vs 77%), G3 vomiting (3% in AC) and G3 diarrhea, desquamation, hand-foot syndrome (3%, 5%, 8% in TX). 56.2% of pts in AC and 63.6% in TX underwent breast conserving op. Conclusions: Primary therapy with TX resulted in higher clinical response and pCR compared with AC in stage II/III BC at this interim analysis. Active accrual will continue and further updates will be presented. Supported by NCC grant-0210150, Aventis Pharma and Roche Korea. No significant financial relationships to disclose.