Phase II study of neoadjuvant gemcitabine, epirubicin, and albumin-bound nab paclitaxel (GEA) in locally advanced breast cancer with SPARC tumor assessments

Abstract

603 Background: Gemcitabine (G), anthracyclines and taxanes have significant activity as neoadjuvant therapy. SPARC, a known prognostic factor for poor survival, is an albumin binding protein that may mediate intratumoral accumulation of nab-paclitaxel (nab-pac) via a SPARC-albumin specific binding activity. This study investigated SPARC tumor status with pathologic correlatives and responses to neoadjuvant chemotherapy. Methods: Eligibility: Clinical T1c-T4-d and/or N0–3, M0 breast cancer (T1N0M0 excluded). ER/PR/HER2 status were obtained for all pts. ECOG PS 0–2, normal LVEF, Treatment: 6 cycles neoadjuvant G 2,000 mg/m2, epirubicin 50 mg/m2, and nab-pac 175 mg/m2 q14 days followed by surgery. Postoperative therapy: 4 cycles G 2,000 mg/m2 and nab-pac 220 mg/m2 q14 days. Myeloid growth factors were mandated with all cycles. Tumor SPARC immunohistochemistry was scored on a 0–3 scale (0=absent, 1= weak, 2=moderate, 3=strong). Fisher's exact test was used for statistical analyses. Results: 123 pts have enrolled with pathologic responses available for 95. 49 pts consented to SPARC testing, 32 pts declined, and 42 are in progress. Median age 51 (29–72). Median tumor size 4.5 cm. Histology: 78% ductal, 9% lobular, 13% others. 42% ER and PR negative. 55% clinical T3/T4 and 66% lymph node positive at presentation. G3/4 toxicity present in >5% of patients: neutropenia 10% (febrile neutropenia 1 pt), thrombocytopenia 5% with arthralgias, fatigue, and infection each in 7%. 20 pts did not complete study treatment for the following reasons: disease progression 7, toxicity 3, patient/MD request 5, and other 5. Total of 1,049 cycles were administered. pCR was noted in 21 pts (22%) with PRs in 69 pts (67%), and 5 SD. SPARC data were available for 44 pts (6 pts- level 0, 5 pts level 1, 14 patients level 2, 19 pts level 3). Pts who were ER+ were more likely to be SPARC+ (p=0.01). Pts who were triple negative were more likely to be SPARC- (p=0.04). Conclusions: Neoadjuvant dose dense GEA demonstrated favorable activity with pathologic response rates comparable to other neoadjuvant regimens albeit with minimal toxicity. Additional data on SPARC analyses are in progress and will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly and Company, Pfizer Abraxis Oncology, Eli Lilly and Company, Pfizer