title: Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer.
abstract: BACKGROUND
  We evaluated AGS-1C4D4, a fully human monoclonal antibody to prostate stem cell antigen (PSCA), with gemcitabine in a randomized, phase II study of metastatic pancreatic cancer.
  
  
  METHODS
  Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and previously untreated, metastatic pancreatic adenocarcinoma were randomly assigned 1:2 to gemcitabine (1000 mg/m(2) weekly seven times, 1 week rest, weekly three times q4weeks) or gemcitabine plus AGS-1C4D4 (48 mg/kg loading dose, then 24 mg/kg q3weeks IV). The primary end point was 6-month survival rate (SR). Archived tumor samples were collected for pre-planned analyses by PSCA expression.
  
  
  RESULTS
  Between April 2009 and May 2010, 196 patients were randomly assigned to gemcitabine (n = 63) or gemcitabine plus AGS-1C4D4 (n = 133). The 6-month SR was 44.4% (95% CI, 31.9-57.5) in the gemcitabine arm and 60.9% (95% CI, 52.1-69.2) in the gemcitabine plus AGS-1C4D4 arm (P = 0.03), while the median survival was 5.5 versus 7.6 months and the response rate was 13.1% versus 21.6% in the two arms, respectively. The 6-month SR was 57.1% in the gemcitabine arm versus 79.5% in the gemcitabine plus AGS-1C4D4 arm among the PSCA-positive subgroup and 31.6% versus 46.2% among the PSCA-negative subgroup.
  
  
  CONCLUSIONS
  This randomized, phase II study achieved its primary end point, demonstrating an improved 6-month SR with addition of AGS-1C4D4 to gemcitabine among patients with previously untreated, metastatic pancreatic adenocarcinoma. ClinicalTrials.gov identifier: NCT00902291.
authors: Dana-Farber Cancer Institute, Boston. Electronic address: bwolpin@partners.org.
authors: B M
authors: BM
authors: Wolpin
authors: Memorial Sloan Kettering Cancer Center, New York, USA.
authors: E M
authors: EM
authors: O'Reilly
authors: Sunnybrook Health Science Center, Toronto, Canada.
authors: Y J
authors: YJ
authors: Ko
authors: Massachusettes General Hospital, Boston.
authors: L S
authors: LS
authors: Blaszkowsky
authors: Kaiser Permanente Northwest Region Oncology Hematology, Portland.
authors: M
authors: M
authors: Rarick
authors: Sylvester Comprehensive Cancer Center, University of Miami, Miami.
authors: C M
authors: CM
authors: Rocha-Lima
authors: Medical College of Wisconsin, Milwaukee.
authors: P
authors: P
authors: Ritch
authors: Vanderbilt University Medical Center, Nashville, USA.
authors: E
authors: E
authors: Chan
authors: Cross Cancer Institute, Edmonton, Alberta, Canada.
authors: J
authors: J
authors: Spratlin
authors: Hospital Vall d'Hebrón, Servicio de Oncología, Barcelona, Spain.
authors: T
authors: T
authors: Macarulla
authors: Juravinski Cancer Centre, Hamilton, Ontario, Canada.
authors: E
authors: E
authors: McWhirter
authors: Inserm U1071, Centre Hospitalier Universitaire Estaing, Clermont-Ferrand, France.
authors: D
authors: D
authors: Pezet
authors: State Institution 'Blokhin Cancer Research Centre RAMS', Moscow.
authors: M
authors: M
authors: Lichinitser
authors: State Healthcare Institution 'Leningrad Regional Oncologic Dispensary', Saint Petersburg, Russia.
authors: L
authors: L
authors: Roman
authors: Agensys, Inc., Santa Monica, USA.
authors: A
authors: A
authors: Hartford
authors: Agensys, Inc., Santa Monica, USA.
authors: K
authors: K
authors: Morrison
authors: Agensys, Inc., Santa Monica, USA.
authors: L
authors: L
authors: Jackson
authors: Agensys, Inc., Santa Monica, USA.
authors: M
authors: M
authors: Vincent
authors: Agensys, Inc., Santa Monica, USA.
authors: L
authors: L
authors: Reyno
authors: Centro Integral Oncológico 'Clara Campal', Madrid; Centro Nacional de Investigaciones Oncologicas, Madrid, Spain.
authors: M
authors: M
authors: Hidalgo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; D003841:Deoxycytidine; C583063:MK-4721; D000093542:Gemcitabine
keywords: chemotherapy; clinical trial; gemcitabine; metastatic disease; pancreatic cancer; prostate stem cell antigen