Phase II study of neoadjuvant bevacizumab and trastuzumab administered with albumin-bound paclitaxel (nab paclitaxel) and carboplatin in HER2+ locally advanced breast cancer

Abstract

627 Background: HER2 signaling up-regulates vascular endothelial growth factor (VEGF) resulting in subsequent tumor angiogenesis and tumor progression. SPARC is a known prognostic factor for poor survival and its expression increases with tumor aggressiveness. SPARC may mediate enhanced intratumoral accumulation of nab paclitaxel (nab-pac) via a SPARC-albumin specific binding activity. This multicenter phase II pilot study was designed to evaluate feasibility, toxicity, and preliminary efficacy of dual VEGF and HER2 receptor blockade with bevacizumab (B) and trastuzumab (T) in combination with neoadjuvant nab-pac and carboplatin. SPARC tumor assessments were performed at baseline. Methods: Eligibility: cT1–4, N0–3, M0 adenocarcinoma, FISH HER2+, normal LVEF, ECOG PS ≤2, adequate organ function, controlled hypertension (HTN), neuropathy ≤ G1, tumor tissue availability for SPARC testing. Treatment: Nab-pac 100mg/m2 weekly days 1, 8, 15 q28 days with carboplatin AUC of 6 day 1 q28 days x 6 cycles, B 5mg/kg qwk x 23 wks with T 4mg/kg loading dose followed by 2mg/kg qwk x 22 wks. Surgery ≥ 4 wks following last B. T at 6mg/kg and B 15mg/kg q3wk post op for a total of 1 year (B began ≥ 4 weeks post op). LVEF at baseline, 3, 6, 12, and 18 months. SPARC IHC was scored on a 0–3 level (0=absent, 1= weak, 2=moderate, 3=strong). Results: 25 pts are evaluable for toxicity. Histology: ductal 80%, lobular 12%. 48% ER-PR-. ECOG PS 0 - 90%. G3/4 toxicity in >5% of patients included: neutropenia 12 pts (48%) and hypertension 3 pts (13%). No LVEF dysfunction was noted. 4 pts went off study: 2 - pt wishes, 2 - toxicity (fatigue, reflux). 2 pts did not complete post op therapy (unrelated to treatment). Complete pathologic responses were noted in 5 pts and PRs in 3 pts. SPARC data were available for 19 pts (1 pt-level 0, 4 pts level 1, 10 pts level 2, 6 pts level 3). Conclusions: Neoadjuvant T plus B with nab paclitaxel and carboplatin is feasible with promising activity. No unexpected toxicities have been reported and there has been no early evidence of LVEF dysfunction. Correlation of SPARC tumor staining with pathologic responses as well as hormone receptor status will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech Abraxis, Genentech