title: SPARC Expression Did Not Predict Efficacy of nab-Paclitaxel plus Gemcitabine or Gemcitabine Alone for Metastatic Pancreatic Cancer in an Exploratory Analysis of the Phase III MPACT Trial.
abstract: OBJECTIVE
  nab-Paclitaxel plus gemcitabine was superior to gemcitabine alone for patients with metastatic pancreatic cancer (MPC) in the phase III MPACT trial. This study evaluated the association of secreted protein acidic and rich in cysteine (SPARC) levels with efficacy as an exploratory endpoint.
  
  
  METHODS
  Patients with previously untreated MPC (N = 861) received nab-paclitaxel plus gemcitabine or gemcitabine alone. Baseline SPARC level was measured in the tumor stroma and epithelia (archival biopsies) and plasma. Experiments were performed in pancreatic cancer mouse models in which SPARC was intact or deleted.
  
  
  RESULTS
  SPARC was measured in the tumor stroma of 256 patients (30%), the tumor epithelia of 301 patients (35%), and plasma of 343 patients (40%). Stroma-evaluable samples were from metastases (71%), from the pancreas (11%), or of unidentifiable origin (insufficient tissue to determine; 17%). For all patients, stromal SPARC level [high (n = 71) vs. low (n = 185)] was not associated with overall survival (OS; HR, 1.019; P = 0.903); multivariate analysis confirmed this lack of association. There was no association between stromal SPARC level and OS in either treatment arm. Neither tumor epithelial SPARC nor plasma SPARC was associated with OS. Results from a SPARC knockout mouse model treated with nab-paclitaxel plus gemcitabine revealed no correlation between SPARC expression and tumor progression or treatment efficacy.
  
  
  CONCLUSIONS
  SPARC levels were not associated with efficacy in patients with MPC. This exploratory analysis does not support making treatment decisions regarding nab-paclitaxel plus gemcitabine or gemcitabine alone in MPC based on SPARC expression.
authors.affiliation: Centro Nacional de Investigaciones Oncologicas, Madrid, Spain. mhidalgo@cnio.es mmusteanu@cnio.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
authors.affiliation: Laboratorio de Dianas Terapeuticas, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Plaza
authors.affiliation: Centro Nacional de Investigaciones Oncologicas, Madrid, Spain. mhidalgo@cnio.es mmusteanu@cnio.es.
authors.forename: Monica
authors.initials: M
authors.lastname: Musteanu
authors.affiliation: Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Peter
authors.initials: P
authors.lastname: Illei
authors.affiliation: Celgene Corporation, Summit, New Jersey.
authors.forename: Carrie B
authors.initials: CB
authors.lastname: Brachmann
authors.affiliation: Celgene Corporation, Summit, New Jersey.
authors.forename: Carla
authors.initials: C
authors.lastname: Heise
authors.affiliation: Celgene Corporation, Summit, New Jersey.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pierce
authors.affiliation: Centro Nacional de Investigaciones Oncologicas, Madrid, Spain.
authors.forename: Pedro P
authors.initials: PP
authors.lastname: Lopez-Casas
authors.affiliation: Centro Nacional de Investigaciones Oncologicas, Madrid, Spain.
authors.forename: Camino
authors.initials: C
authors.lastname: Menendez
authors.affiliation: Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: Celgene Corporation, Boudry, Switzerland.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Romano
authors.affiliation: Celgene Corporation, Summit, New Jersey.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wei
authors.affiliation: Laboratorio de Dianas Terapeuticas, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Lopez-Rios
authors.affiliation: Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, Arizona.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
mesh_terms: D000418:Albumins / Q000008:administration & dosage; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D015676:Osteonectin / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D015415:Biomarkers; D015676:Osteonectin; C577241:SPARC protein, human; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine