title: A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin alpha(v)beta(3), + or - dacarbazine in patients with stage IV metastatic melanoma.
abstract: BACKGROUND
  The alpha (v) beta (3) (alpha(v)beta(3)) integrin is involved in intracellular signaling regulating cell proliferation, migration, and differentiation and is important for tumor-induced angiogenesis.
  
  
  METHODS
  This phase 2, randomized, open-label, 2-arm study was designed to capture safety data and evaluate the antitumor efficacy of etaracizumab (Abegrin), an IgG1 humanized monoclonal antibody against the alpha(v)beta(3) integrin, in patients with previously untreated metastatic melanoma. The objective was to evaluate whether etaracizumab + or - dacarbazine had sufficient clinical activity to warrant further study in a phase 3 clinical trial.
  
  
  RESULTS
  One hundred twelve patients were randomized to receive etaracizumab alone (N = 57) or etaracizumab + dacarbazine (N = 55). Safety of etaracizumab + or - dacarbazine was acceptable with infusion-related, gastrointestinal, and metabolic reactions being the most common adverse events (AEs). The majority of AEs were grade 1 or 2 in severity in both study arms; most events were not considered serious, except for cardiovascular (myocardial infarction, atrial fibrillation) and thromboembolic events, which occurred in 3 and 5 patients, respectively. None of the patients in the etaracizumab-alone study arm and 12.7% of patients in the etaracizumab + dacarbazine study arm achieved an objective response. The median duration of objective response in the etaracizumab + dacarbazine study arm was 4.2 months. Stable disease rate, time to progression (TTP), and progression-free survival (PFS) appeared to be similar between the 2 treatment arms. Stable disease occurred in 45.6% of patients in the etaracizumab-alone study arm and 40.0% of patients in the etaracizumab + dacarbazine study arm. Median TTP and median PFS were both 1.8 months in the etaracizumab-alone study arm and 2.5 and 2.6 months in the etaracizumab + dacarbazine study arm, respectively. Median overall survival was 12.6 months in the etaracizumab-alone study arm and 9.4 months in the etaracizumab + dacarbazine study arm.
  
  
  CONCLUSIONS
  The survival results in both treatment arms of this study were considered unlikely to result in clinically meaningful improvement over dacarbazine alone.
authors.affiliation: Newcastle Melanoma Unit, Newcastle, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Hersey
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sosman
authors.forename: Steven
authors.initials: S
authors.lastname: O'Day
authors.forename: Jon
authors.initials: J
authors.lastname: Richards
authors.forename: Agop
authors.initials: A
authors.lastname: Bedikian
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.forename: William
authors.initials: W
authors.lastname: Sharfman
authors.forename: Robert
authors.initials: R
authors.lastname: Weber
authors.forename: Theodore
authors.initials: T
authors.lastname: Logan
authors.forename: Manuela
authors.initials: M
authors.lastname: Buzoianu
authors.forename: Luz
authors.initials: L
authors.lastname: Hammershaimb
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D039302:Integrin alphaVbeta3; C112567:etaracizumab; D003606:Dacarbazine