title: Selection of immunostimulant AS15 for active immunization with MAGE-A3 protein: results of a randomized phase II study of the European Organisation for Research and Treatment of Cancer Melanoma Group in Metastatic Melanoma.
abstract: OBJECTIVE
  Active immunization against the tumor-specific MAGE-A3 antigen is followed by a few but impressive and durable clinical responses. This randomized phase II trial evaluated two different immunostimulants combined with the MAGE-A3 protein to investigate whether a more robust and persistent immune response could be associated with increased clinical benefit.
  
  
  METHODS
  Patients with MAGE-A3-positive stage III or IV M1a melanoma were randomly assigned to receive the MAGE-A3 protein combined either with AS02B or with AS15 immunostimulant. Clinical end points were toxicity and rates of objective clinical responses, progression-free survival (PFS), and overall survival (OS).
  
  
  RESULTS
  Seventy-five patients were treated, with 36 eligible patients per arm. Both treatments were well tolerated. In the AS15 arm, four objective responses were observed (three complete responses and one partial response) versus one partial response in the AS02B arm. In the AS15 and AS02B arms, the PFS rates after 6 months were 25% and 14%, respectively; and the median OS times were 33 months and 19.9 months, respectively, with a median observation period of 48 months. Antibodies against MAGE-A3, found in all patients, showed three-fold higher titers in the AS15 arm. The anti-MAGE-A3 cellular response was also more pronounced in the AS15 arm.
  
  
  CONCLUSIONS
  In the MAGE-A3+AS15 arm, clinical activity was higher and the immune response more robust. Therefore, the AS15 immunostimulant was selected for combination with the MAGE-A3 protein in phase III trials.
authors.affiliation: Department of Internal Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, the Netherlands. w.kruit@erasmusmc.nl
authors.forename: Wim H J
authors.initials: WH
authors.lastname: Kruit
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dreno
authors.forename: Laurent
authors.initials: L
authors.lastname: Mortier
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.forename: Vanna
authors.initials: V
authors.lastname: Chiarion-Sileni
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Testori
authors.forename: Thierry
authors.initials: T
authors.lastname: Dorval
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Grob
authors.forename: Juergen C
authors.initials: JC
authors.lastname: Becker
authors.forename: Alan
authors.initials: A
authors.lastname: Spatz
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Jamila
authors.initials: J
authors.lastname: Louahed
authors.forename: Frédéric F
authors.initials: FF
authors.lastname: Lehmann
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Brichard
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology* / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D011994:Recombinant Proteins