National Comprehensive Cancer Network



About NCCN

Neoadjuvant Bevacizumab with Weekly Nanoparticle Albumin Bound Nab-Paclitaxel Plus Carboplatin Followed by Doxorubicin Plus Cyclophosphamide (AC) for Triple-Negative Breast Cancer

Citation: J Clin Oncol 28:7s, 2010 (suppl; abstr TPS100)

Author(s): J. C. Sachdev, L. E. Kronish, S. West, L. Schwartzberg, M. Jahanzeb; University of Tennessee Cancer Institute, Memphis, TN; Aptium Oncology, Boca Raton Comprehensive Cancer Center, Boca Raton, FL; The West Clinic, Memphis, TN

Abstract:

Background: Triple-negative breast cancers (TNBC) cluster with "basal like" subtype on genomic profiling. Overexpression 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-caveolin 1 interaction. SPARC entraps the albumin resulting in higher intratumoral accumulation and 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 like tumors, we hypothesize that nab-paclitaxel plus the DNA damaging drug carboplatin would demonstrate high response rates in TNBC. Bevacizumab may further enhance efficacy by blocking angiogenesis. Patients with TNBC who achieve a pathologic complete remission (pCR) to neoadjuvant treatment have a better disease-free survival (DFS) than those with less than a pCR. 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. The primary endpoint is pCR, defined as the absence of invasive tumor cells in the breast specimen. The planned sample size is 60, assuming a null hypothesis pCR rate of 25% vs. 40% for the alternate hypothesis. 10 patients have been accrued to date. Patients receive carboplatin AUC 6 day 1 and nab-paclitaxel 100 mg/m2 days 1, 8 and 15 of a 28-day cycle for 4 cycles followed by dose dense AC for 4 cycles. Bevacizumab is given at 10 mg/kg Q 2 weeks with chemotherapy for the first 6 cycles. Definitive surgical resection and radiation therapy 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 on fresh tissue will be undertaken for correlation with response.

Quick Links


About NCCN| NCCN Member Institutions| Patient Resources| NCCN Foundation| Privacy Policy| Legal Notices| Contact Us

275 Commerce Drive, Suite 300, Fort Washington, PA 19034 • 215.690.0300 • Fax: 215.690.0280
Copyright © 2013 National Comprehensive Cancer Network, All Rights Reserved