Neoadjuvant bevacizumab with weekly nab-paclitaxel plus carboplatin followed by doxorubicin plus cyclophosphamide (AC) for triple-negative breast cancer.

Abstract

TPS1137 Background: Triple negative breast cancer (TNBC) predominantly clusters with “basal like” subtype on genomic profiling. Over-expression of Secreted Protein Acidic and Rich in Cysteine (SPARC) has been observed in basal like breast cancer (Charaffe-Jaufrett et al. Oncogene 2006; 2273-84). Endothelial transcytosis of nab- paclitaxel occurs via albumin- gp60 receptor-caveolin 1 interaction. SPARC entraps the albumin resulting in higher intratumoral accumulation, which may explain the increased efficacy of nab-paclitaxel (Desai et al. Translational Oncology 2009; 59-63). Exploiting this mechanism and the dysfunctional BRCA mediated DNA repair in basal tumors, we hypothesize that nab-paclitaxel + the DNA damaging drug carboplatin would produce high response rates in TNBC. Adding bevacizumab may enhance efficacy by blocking angiogenesis. In TNBC, pathologic complete remission (pCR) to neo-adjuvant therapy correlates with better disease-free survival (DFS). We hypothesize that high pCR rates can be achieved for patients with TNBC with this combination translating to an improved DFS than seen historically. Methods: Patients with palpable and operable TNBC ≥ 2 cm are eligible for this single stage phase II trial. pCR (defined as the absence of invasive tumor cells) in the breast is the primary end point, while pCR in the breast + axillary nodes and pCR + near pCR (residual tumor < 5mm) in the breast are secondary end points. 57 evaluable patients are needed, assuming a pCR rate of 25% vs. 40% for the null and alternate hypotheses respectively. 34 patients have been accrued to date. Patients receive carboplatin AUC 6 day 1 and nab-paclitaxel 100mg/m2 days 1, 8 and 15 of a 28 day cycle for 4 cycles and then dose dense AC for 4 cycles. Bevacizumab is given at 10mg/kg Q 2 weeks with chemotherapy for the first 6 cycles. Surgery and radiation are per institutional standards. Bevacizumab is continued postoperatively to complete 1 year of treatment. A core biopsy for collection of fresh tumor tissue is required prior to the start of study treatment. Blood is collected at baseline, and after 4 and 8 cycles for biomarker analysis. Gene expression profiling will be undertaken for correlation with response.