Phase I/II trial of neoadjuvant sunitinib administered with weekly paclitaxel/carboplatin in patients with locally advanced triple-negative breast cancer.

The purpose of the study is to evaluate the feasibility and efficacy of adding sunitinib to paclitaxel/carboplatin in the neoadjuvant therapy of patients with triple-negative breast cancer (TNBC). Patients had histologically proven, previously untreated, triple-negative adenocarcinoma, with disease limited to the breast and axilla (clinical T1-T3, N0-N2, M0; T1N1M0 excluded). Following determination of the maximum tolerated doses in the phase I portion, patients in the phase II study received paclitaxel 70 mg/m(2) IV days 1, 8, and 15; carboplatin AUC 5.0 IV day 1; sunitinib 25 mg orally daily; treatment was administered for six 28-day cycles followed by definitive surgery. Sunitinib was resumed postoperatively to complete a 52-week course. Pathologic complete response (pCR) rate was the primary endpoint. Fifty-four patients enrolled; 41 received treatment in the phase II study. Sixteen patients (39 %) were able to complete six cycles of neoadjuvant therapy; 18 additional patients had surgery after completing 2-5 cycles of treatment. The pCR rate in these 34 evaluable patients was 35 %. The toxicity of the regimen was considerable, with myelosuppression resulting in numerous dose reductions and/or omissions of paclitaxel and carboplatin. Eleven patients (27 %) discontinued sunitinib during neoadjuvant therapy, and six patients (14 %) completed 52 weeks of single-agent sunitinib. In the neoadjuvant treatment of patients with TNBC, the combination of paclitaxel, carboplatin, and sunitinib was difficult to administer, and produced a pCR rate comparable to other less toxic regimens. This combination is not recommended for further evaluation. At present, sunitinib has no defined role in the treatment of breast cancer.