Correlation of SPARC, ER, PR, and HER2 tumor with progression-free survival from a phase II neoadjuvant trial of gemcitabine, epirubicin, and nab-paclitaxel

Autor: John D. Zubkus, Brooke R. Daniel, D. Knauer, Y. Naot, R. C. Inhorn, Cassie M. Lane, D. A. Yardley, Vuong Trieu, Davey B. Daniel, Neil P. Desai
Rok vydání: 2009
Předmět:
Zdroj: Journal of Clinical Oncology. 27:618-618
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2009.27.15_suppl.618
Popis: 618 Background: Neoadjuvant combinations of gemcitabine (G), anthracyclines and taxanes have demonstrated substantial activity with pCR rates of 20–25%. 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 binding activity and is a poor prognostic factor for survival. This study was designed to evaluate the feasibility and safety of a biweekly schedule of neoadjuvant nab paclitaxel (nab-P) with G and epirubicin (E) with SPARC tumor assessments performed in consenting patients (pts). Methods: Eligibility: Clinical T1c-T4d and/or N0–3, M0 breast cancer (T1N0M0 excluded), normal LVEF. ER/PR/HER-2 obtained for all pts. Treatment: neoadjuvant G 2,000 mg/m2, E 50 mg/m2, and nab-P 175 mg/m2 q14 days x 6 cycles followed by surgery. Post operative therapy: G 2,000 mg/m2 and nab-P 220 mg/m2 q14 days x 4 cycles. Myeloid growth factors were mandated with all cycles. Two different antibody reagents were used to probe for SPARC expression of tumoral SPARC and stromal SPARC; level 3 immunohistochemical (IHC) SPARC staining was considered positive. Results: 123 pts enrolled. Pathologic responses are available for 112 pts with 11 unevaluable. 82 pts consented to SPARC tumor testing. Median age 51 (29–72). Median tumor size 4.5 cm. 42% ER-/PR -. 55% clinical T3/T4 and 66% node positive. Pathologic complete responses (pCR) were noted in 22 pts (18%) with PRs in 84 pts (68%), and 6 SD (5%). SPARC IHC staining was available in 77 tumor samples; SPARC positivity was noted in 89% of evaluated tumors achieving pCR. Triple negative, ER negative or PR negative tumors were associated with worse PFS. SPARC + tumors showed a trend to improved PFS that was strongly associated with tumoral SPARC but not stromal SPARC. Conclusions: Dose dense neoadjuvant G, E, and nab-P is active and well tolerated with a favorable pCR rate of 20%. ER neg, PR neg, and triple negative tumors were associated with worse PFS. Despite literature reports of SPARC positivity associated with poor prognosis, SPARC+ tumors in this study showed a high concordance with tumor response and a trend to improved PFS with tumoral SPARC. [Table: see text]
Databáze: OpenAIRE
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