title: A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial.
abstract: BACKGROUND
  This double-blind, phase 3 study assessed the efficacy and safety of ganitumab combined with gemcitabine as first-line treatment of metastatic pancreatic cancer.
  
  
  METHODS
  Patients with previously untreated metastatic pancreatic adenocarcinoma were randomly assigned 2 : 2 : 1 to receive intravenous gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) plus placebo, ganitumab 12 mg/kg, or ganitumab 20 mg/kg (days 1 and 15 of each cycle). The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), safety, and efficacy by levels of circulating biomarkers.
  
  
  RESULTS
  Overall, 322 patients were randomly assigned to placebo, 318 to ganitumab 12 mg/kg, and 160 to ganitumab 20 mg/kg. The study was stopped based on results from a preplanned futility analysis; the final results are reported. Median OS was 7.2 months [95% confidence interval (CI), 6.3-8.2] in the placebo arm, 7.0 months (95% CI, 6.2-8.5) in the ganitumab 12-mg/kg arm [hazard ratio (HR), 1.00; 95% CI, 0.82-1.21; P = 0.494], and 7.1 months (95% CI, 6.4-8.5) in the ganitumab 20-mg/kg arm (HR, 0.97; 95% CI, 0.76-1.23; P = 0.397). Median PFS was 3.7, 3.6 (HR, 1.00; 95% CI, 0.84-1.20; P = 0.520), and 3.7 months (HR, 0.97; 95% CI, 0.77-1.22; P = 0.403), respectively. No unexpected toxicity was observed with ganitumab plus gemcitabine. The circulating biomarkers assessed [insulin-like growth factor-1 (IGF-1), IGF-binding protein-2, and -3] were not associated with a treatment effect on OS or PFS by ganitumab.
  
  
  CONCLUSIONS
  Ganitumab combined with gemcitabine had manageable toxicity but did not improve OS, compared with gemcitabine alone in unselected patients with metastatic pancreatic cancer.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01231347.
authors.affiliation: Department of Medical Oncology/Solid Tumor Oncology, Dana-Farber Cancer Institute, Boston, USA. Electronic address: charles_fuchs@dfci.harvard.edu.
authors.forename: C S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Oncology Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: Azevedo
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Okusaka
authors.affiliation: Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium.
authors.forename: J-L
authors.initials: JL
authors.lastname: Van Laethem
authors.affiliation: Medical Oncology, Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: L R
authors.initials: LR
authors.lastname: Lipton
authors.affiliation: Department of Hematology, Oncology, and Tumor Immunology, Charité University, Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Riess
authors.affiliation: Department of Oncology, Military Institute of Health Services, Warsaw, Poland.
authors.forename: C
authors.initials: C
authors.lastname: Szczylik
authors.affiliation: Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
authors.forename: M J
authors.initials: MJ
authors.lastname: Moore
authors.affiliation: Department of Oncology, Antwerp University Hospital, Edegum, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Department of Oncology, St László Hospital, Budapest, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Bodoky
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc.
authors.forename: B
authors.initials: B
authors.lastname: Melichar
authors.affiliation: Department of Oncology, Masaryk University Medical School and Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: R
authors.initials: R
authors.lastname: Nemecek
authors.affiliation: Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ohkawa
authors.affiliation: Department of Haematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Świeboda-Sadlej
authors.affiliation: Department of Clinical Pharmacology and Chemotherapy, Russian Cancer Research Center, Moscow, Russia.
authors.forename: S A
authors.initials: SA
authors.lastname: Tjulandin
authors.affiliation: Digestive Oncology, University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Van Cutsem
authors.affiliation: Medical Sciences, Amgen Inc., Thousand Oaks, USA.
authors.forename: R
authors.initials: R
authors.lastname: Loberg
authors.affiliation: Global Biostatistical Science, Amgen Ltd, Cambridge, UK.
authors.forename: V
authors.initials: V
authors.lastname: Haddad
authors.affiliation: Global Development, Thousand Oaks.
authors.forename: J L
authors.initials: JL
authors.lastname: Gansert
authors.affiliation: Development Oncology Therapeutics, Amgen Inc., Thousand Oaks, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Bach
authors.affiliation: Medical Oncology Department, University Hospital Ramon y Cajal, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Carrato
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D003841:Deoxycytidine; C545764:ganitumab; D000093542:Gemcitabine
keywords: IGF-1 receptor; biomarker; ganitumab; gemcitabine; pancreatic cancer