Randomized phase II study of weekly paclitaxel with and without carboplatin followed by cyclophosphamide/epirubicin/5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA breast cancer without HER2 overexpression

Addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast cancer may improve pathological complete response (pCR) rates. We evaluated the efficacy and safety of carboplatin and weekly paclitaxel (wPTX) followed by cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) as neoadjuvant chemotherapy for HER2-negative breast cancer. Patients with stage II/IIIA HER2-negative breast cancer were randomly assigned to preoperatively receive CP-CEF (four 3-week cycles of carboplatin [area under the curve 5 mg/mL/min, day 1] and wPTX [80 mg/m², day 1, 8, 15] followed by four 3-week cycles of CEF [500/100/500 mg/m²] or P-CEF (four cycles of wPTX followed by four cycles of CEF). The primary objective was pCR rate. Of 181 eligible patients, 89 were randomly assigned to the CP-CEF and 92 to the P-CEF. Two patients in each arm refused to receive neoadjuvant chemotherapy. Overall 88 patients in the CP-CEF and 91 patients in the P-CEF were assessable for efficacy and safety. The pCR rate in the CP-CEF was significantly higher than that in the P-CEF (31.8 vs. 17.6 %, one-sided P = 0.01). Among patients with triple-negative breast cancer, the pCR rate in the CP-CEF was significantly higher than that in the P-CEF [61.2 (23/37) vs. 26.3 % (10/38), P = 0.003]. Grade 3–4 neutropenia was observed in the CP-CEF more frequently than in the P-CEF (65.9 vs. 38.5 %). Adding carboplatin to neoadjuvant wPTX followed by CEF for HER2-negative breast cancer improved the pCR rate and exacerbated hematotoxicity.