title: Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase II randomized study results.
abstract: OBJECTIVE
  The MAGE-A3 protein is expressed in approximately 35% of patients with resectable non-small-cell lung cancer (NSCLC). Several immunization approaches against the MAGE-A3 antigen have shown few, but often long-lasting, clinical responses in patients with metastatic melanoma.
  
  
  METHODS
  A double-blind, randomized, placebo-controlled phase II study was performed assessing clinical activity, immunologic response, and safety following immunization with recombinant MAGE-A3 protein combined with an immunostimulant (13 doses over 27 months) in completely resected MAGE-A3-positive stage IB to II NSCLC. The primary end point was disease-free interval (DFI).
  
  
  RESULTS
  Patients were randomly assigned to either MAGE-A3 immunotherapeutic (n = 122) or placebo (n = 60). After a median postresection period of 44 months, recurrence was observed in 35% of patients in the MAGE-A3 arm and 43% in the placebo arm. No statistically significant improvement in DFI (hazard ratio [HR], 0.75, 95% CI, 0.46 to 1.23; two-sided P = .254), disease-free survival (DFS; HR, 0.76; 95% CI, 0.48 to 1.21; P = .248), or overall survival (HR, 0.81; 95% CI, 0.47 to 1.40; P = .454) was observed. Corresponding analysis after a median of 70 months of follow-up revealed a similar trend for DFI and DFS. All patients receiving the active treatment showed a humoral immune response to the MAGE-A3 antigen, although no correlation was observed with outcome. No significant toxicity was observed.
  
  
  CONCLUSIONS
  In this early development study with a limited number of patients, postoperative MAGE-A3 immunization proved to be feasible with minimal toxicity. These results are being investigated further in a large phase III study.
authors.affiliation: University HospitalKU Leuven, Leuven, Belgium. johan.vansteenkiste@uzleuven.be
authors.forename: Johan
authors.initials: J
authors.lastname: Vansteenkiste
authors.forename: Marcin
authors.initials: M
authors.lastname: Zielinski
authors.forename: Albert
authors.initials: A
authors.lastname: Linder
authors.forename: Jubrail
authors.initials: J
authors.lastname: Dahabreh
authors.forename: Emilio E
authors.initials: EE
authors.lastname: Gonzalez
authors.forename: Wojciech
authors.initials: W
authors.lastname: Malinowski
authors.forename: Marta
authors.initials: M
authors.lastname: Lopez-Brea
authors.forename: Tonu
authors.initials: T
authors.lastname: Vanakesa
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.forename: Haralabos
authors.initials: H
authors.lastname: Kalofonos
authors.forename: Jakub
authors.initials: J
authors.lastname: Perdeus
authors.forename: Reiner
authors.initials: R
authors.lastname: Bonnet
authors.forename: Jazeps
authors.initials: J
authors.lastname: Basko
authors.forename: Richard
authors.initials: R
authors.lastname: Janilionis
authors.forename: Bernward
authors.initials: B
authors.lastname: Passlick
authors.forename: Tom
authors.initials: T
authors.lastname: Treasure
authors.forename: Marc
authors.initials: M
authors.lastname: Gillet
authors.forename: Frédéric F
authors.initials: FF
authors.lastname: Lehmann
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Brichard
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D009363:Neoplasm Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D011994:Recombinant Proteins