title: Adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation after resection of primary tumor > 1.5 mm in patients with stage II melanoma: results of the EORTC 18961 randomized phase III trial.
abstract: OBJECTIVE
  The GM2 ganglioside is an antigen expressed in the majority of melanomas. The GM2-KLH/QS-21 vaccine induces high immunoglobulin M (IgM) and IgG antibody responses. The EORTC 18961 trial compared the efficacy of GM2-KLH/QS-21 vaccination versus observation.
  
  
  METHODS
  A total of 1,314 patients with a primary tumor > 1.50 mm in thickness (T3-4N0M0; American Joint Committee on Cancer stage II) were randomly assigned to GM2-KLH/QS-21 vaccination (n = 657) or observation (n = 657). Treatment consisted of subcutaneous injections once per week from week 1 to 4, then every 3 months for the first 2 years and every 6 months during the third year. Primary end point was relapse-free survival (RFS). Secondary end points were distant metastasis-free survival (DMFS) and overall survival (OS). Analyses were by intent to treat.
  
  
  RESULTS
  After a median follow-up of 1.8 years, the trial was stopped at the second interim analysis for futility regarding RFS (hazard ratio [HR], 1.00; P = .99) and detrimental outcome regarding OS (HR, 1.66; P = .02). After a median follow-up of 4.2 years, we had recorded 400 relapses, nine deaths without relapse, a total of 236 deaths. At 4 years, the vaccination arm showed a decreased RFS rate of 1.2% (HR, 1.03; 95% CI, 0.84 to 1.25) and OS rate of 2.1% (HR, 1.16; 95% CI, 0.90 to 1.51). Toxicity was acceptable, with 4.6% of patients ending study participation because of toxicity.
  
  
  CONCLUSIONS
  GM2-KLH/QS-21 vaccination does not improve outcome for patients with stage II melanoma.
authors.affiliation: Alexander M.M. Eggermont, Institut de Cancérologie Gustave Roussy, Villejuif, Paris-Sud, and Université Paris-Sud, Kremlin Bicêtre, Paris, France; Stefan Suciu, Larissa Polders, and Michel Praet, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Piotr Rutkowski, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; Jeremy Marsden, University Hospital Birmingham, Birmingham; Philippa Corrie, Addenbrookes Hospital, Cambridge; Poulam M. Patel, University of Nottingham, Nottingham; Neville Davidson, Broomfield Hospital, Broomfield, United Kingdom; Mario Santinami, Istituto Nazionale dei Tumori, Milan; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione Pascale, Napoli; Lorenzo Borgognoni, Istituto Tumori Toscano, S. Maria Annunziata Hospital, Florence; Maria Grazia Bernengo, University Hospital Turin, Turin, Italy; Steinar Aamdal, Oslo University Hospital and Radium Hospital, Oslo, Norway; Wim H. Kruit, Erasmus University Medical Center-Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Lars Bastholt, Odense University Hospital, Odense, Denmark; and Alan Spatz, McGill University and Lady Davis Institute for Medical Research, Montreal, Quebec, Canada.
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Piotr
authors.initials: P
authors.lastname: Rutkowski
authors.forename: Jeremy
authors.initials: J
authors.lastname: Marsden
authors.forename: Mario
authors.initials: M
authors.lastname: Santinami
authors.forename: Philippa
authors.initials: P
authors.lastname: Corrie
authors.forename: Steinar
authors.initials: S
authors.lastname: Aamdal
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
authors.forename: Poulam M
authors.initials: PM
authors.lastname: Patel
authors.forename: Wim H
authors.initials: WH
authors.lastname: Kruit
authors.forename: Lars
authors.initials: L
authors.lastname: Bastholt
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Borgognoni
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Bernengo
authors.forename: Neville
authors.initials: N
authors.lastname: Davidson
authors.forename: Larissa
authors.initials: L
authors.lastname: Polders
authors.forename: Michel
authors.initials: M
authors.lastname: Praet
authors.forename: Alan
authors.initials: A
authors.lastname: Spatz
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D005678:G(M2) Ganglioside / Q000627:therapeutic use*; D006433:Hemocyanins / Q000627:therapeutic use*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000473:pathology* / Q000517:prevention & control / Q000601:surgery*; D008875:Middle Aged; D009367:Neoplasm Staging; D012503:Saponins / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology* / Q000517:prevention & control / Q000601:surgery*; D057832:Watchful Waiting
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D012503:Saponins; D005678:G(M2) Ganglioside; C078785:saponin QA-21V1; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin