N0338 phase II trial of docetaxel and carboplatin administered every two weeks as induction therapy for stage II or III breast cancer

563 Background: Neoadjuvant chemotherapy is increasingly used in the treatment of stage II/III breast cancer (BC). Pathologic complete response (pCR) after neoadjuvant therapy is associated with improved clinical outcome. Based on activity of docetaxel (D) and carboplatin (C) in metastatic BC, we investigated a dose-dense schedule of D and C combination for neoadjuvant therapy of patients with stage II/III BC. Methods: A two-stage phase II study was conducted with pCR (disappearance of all invasive tumor from breast and axilla) rate as the primary endpoint. Rate of breast-conserving surgery, clinical response rate, and toxicity were secondary endpoints. Pts with stage II/III BC, > 18 y, ECOG PS 0–1, and adequate organ function were eligible. Treatment consisted of 4 cycles of D 75 mg/m2 and C AUC=6 on day 1 and pegfilgrastim 6mg SQ on day 2 of a 14 day cycle. The study required 55 evaluable patients to test the null hypothesis that pCR rate was at most 15% against the alternative of at least 30%. Results: Fifty-seven women were enrolled between Sept, 05 and June, 07. All patients were evaluable. Median age 53 y (27–79y). 38 (67%) had ER+, 31 (54%) PR+,6 (11%) HER2+; 9 had ER/PR and HER2 neg BC A median of 4 (1–4) cycles were administered. 3 (6%) pts progressed during treatment, 3 (6%) discontinued treatment because of toxicity, and 3 (6%) for other reasons. Nine (16%, 90% CI :10%-28%) patients had pCR; 2 pts had only DCIS and 1 had nodal disease only at surgery. 4 of 9 (44%) pts with ER/PR and HER2 neg BC had pCR 43 (75%, 95%CI: 62%-86%) out of 57 eligible patients had clinical response (15 cCR, 28cPR). 48 (87%, 95% CI:72%-93%) patients had breast-conserving surgery. The median dose administered was 75 mg/m2 for D and AUC=6 for C for cycles 1–4. The most common gr 3/4 adverse events (AE) were thrombocytopenia 11 (19%), fatigue 7 (12%) and anemia 5 (9%). 54% (31/57) and 9% of patients had gr 3 and 4 AE. Conclusions: 4 cycles of bi-weekly D and C are feasible and tolerable and result in pCR rate of 16%. This regimen can be considered for neoadjuvant treatment of BC, especially in patients not suitable for anthracycline therapy. Immune and molecular predictors of efficacy are being evaluated. Partially supported by NIH CA25224 No significant financial relationships to disclose.