Preliminary progression free survival and SPARC tumor correlatives from a phase II neoadjuvant trial of gemcitabine, epirubicin, and nab paclitaxel.

Abstract

Abstract Abstract #5116 Background: Neoadjuvant combinations of gemcitabine (G), anthracyclines and taxanes have demonstrated significant activity with pCR rates of 20-25% albeit with significant myelosuppression. Secreted protein acidic rich in cysteine (SPARC) is an albumin binding protein that mediates intratumoral accumulation of nab-paclitaxel (nab-P) via a SPARC-albumin specific binding activity. This study was designed to evaluate a biweekly schedule of neoadjuvant nab paclitaxel (nab-P) with gemcitabine and epirubicin (E). SPARC tumor assessments were performed in consenting patients (pts) with subsequent pathologic and survival correlatives.
 Methods: Eligibility: Clinical T1c-T4d and/or N0-3, M0 breast cancer (T1N0M0 excluded), ECOG PS 0-2, normal LVEF. ER/PR/HER2 obtained for all pts. Treatment: 6 cycles neoadjuvant G 2000 mg/m2, E 50 mg/m2, and nab-P 175 mg/m2 q14 days followed by surgery. Post operative therapy: 4 cycles G 2000 mg/m2 and nab-P 220 mg/m2 q14 days. Myeloid growth factors were mandated with all cycles. 2 antibody reagents were used to probe for SPARC expressions. For this study, level 3 immunohistochemical (IHC) SPARC staining was considered positive. Results: 123 pts have enrolled with pathologic responses available for 106. 82 pts consented to SPARC testing. Median age 51 (29-72). Median tumor size 4.5 cm. Histology: 81% ductal, 10% lobular, 9% other. 42% ER and PR negative. 55% clinical T3/T4 and 66% lymph node positive at presentation. G3/4 toxicity present in >5% of pts: neutropenia 16% (febrile neutropenia 1 pt), thrombocytopenia 9% with arthralgias 11%, fatigue 10%, and infection 7%. 20 pts did not complete study treatment for the following reasons: disease progression 7, toxicity 3, pt/MD request 5, and other 5. pCR was noted in 23 pts (22%) with PRs in 76 pts (71%), and 6 SD. SPARC IHC staining was available for 76 tumors. SPARC level 3 IHC staining was noted in 65 tumors (86%); 65% were associated with a PR or pCR. Median PFS was 23 months and overall survival at 24 months is 77%. Pts who relapsed ≤16 months from diagnosis were more likely to be triple negative (p = 0.04), or ER negative (p = 0.001), or PR negative (p = 0.0006). Conclusions: Neoadjuvant dose dense GEA is active and better tolerated than other gemcitabine/anthracycline/taxane combinations. The pCR rate of 22% compares favorably with other comparable neoadjuvant regimens albeit with minimal toxicity. Pts with early relapse defined as ≤16 months from diagnosis were more likely to demonstrate a triple negative phenotype or demonstrate estrogen or progesterone receptor negativity. SPARC tumor correlatives with progression free and overall survival are on ongoing and will be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5116.