title: Human equilibrative nucleoside transporter 1 is not predictive for gemcitabine efficacy in advanced pancreatic cancer: translational results from the AIO-PK0104 phase III study with the clone SP120 rabbit antibody.
abstract: BACKGROUND
  The role of human equilibrative nucleoside transporter 1 (hENT1) as a predictive biomarker for gemcitabine efficacy in advanced pancreatic cancer remains unclear to date.
  
  
  METHODS
  AIO-PK0104 was a German multicenter phase III trial comparing gemcitabine/erlotinib followed by capecitabine (GEC) with capecitabine/erlotinib followed by gemcitabine (CEG) in advanced pancreatic cancer. Archival tumour tissue from 169 of the 274 eligible study patients was available for a central and standardised immunohistochemistry staining for hENT1 expression using the SP120 rabbit monoclonal anti-hENT1 antibody. Within a retrospective translational subgroup analysis, biomarker data were correlated with efficacy end-points.
  
  
  RESULTS
  Thirty-nine out of 130 fresh-cut slides were scored as hENT1(high) (30%), whereas 91 samples were classified as hENT1(low) (70%). For the 62 patients randomised to CEG median overall survival was estimated with 6.4 months in the hENT1(low) compared to 6.9 months in the hENT1(high) subgroup (Hazard Ratio (HR) 0.88, 95% confidence interval (CI) 0.48-1.61, p=0.67). For the 68 patients randomised to GEC survival was 5.7 months in the hENT1(low) compared to 4.4 months in the hENT1(high) subgroup (HR 1.16, 95% CI 0.69-1.96, p=0.57). In 101 patients receiving gemcitabine at any time during study treatment (either within the 1st- or 2nd-line setting) hENT1(low) cases had a median overall survival of 7.5 months and hENT1(high) patients an overall survival of 4.4 months (HR 1.30, 95% CI 0.84-2.03, p=0.24), respectively.
  
  
  CONCLUSIONS
  Within this subgroup analysis from Arbeitsgemeinschaft Internistische Onkologie-pancreatic cancer (AIO-PK0104), no evidence supporting the use of hENT1 as a predictive biomarker for gemcitabine efficacy in patients with advanced pancreatic cancer was found.
authors.affiliation: Department of Pathology, Ludwig-Maximilians-University of Munich, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Ormanns
authors.affiliation: Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
authors.affiliation: Clovis Oncology Inc., San Francisco, CA, USA.
authors.forename: Mitch
authors.initials: M
authors.lastname: Raponi
authors.affiliation: Clovis Oncology Inc., San Francisco, CA, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Isaacson
authors.affiliation: German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Germany.
authors.forename: Rüdiger P
authors.initials: RP
authors.lastname: Laubender
authors.affiliation: Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Haas
authors.affiliation: Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Kruger
authors.affiliation: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Kleespies
authors.affiliation: Clovis Oncology Inc., San Francisco, CA, USA.
authors.forename: Elaina
authors.initials: E
authors.lastname: Mann
authors.affiliation: Clovis Oncology Inc., San Francisco, CA, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Bartosiewicz
authors.affiliation: Department of Pathology, Ludwig-Maximilians-University of Munich, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.affiliation: Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany. Electronic address: stefan.boeck@med.uni-muenchen.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Boeck
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D033721:Equilibrative Nucleoside Transporter 1 / Q000032:analysis / Q000096:biosynthesis*; D000069347:Erlotinib Hydrochloride; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage; D011817:Rabbits; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D033721:Equilibrative Nucleoside Transporter 1; D011799:Quinazolines; C438649:SLC29A1 protein, human; D003841:Deoxycytidine; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; D005472:Fluorouracil; D000093542:Gemcitabine
keywords: Gemcitabine; Pancreatic cancer; hENT1