Alexander M M Eggermont1, Stefan Suciu, Piotr Rutkowski, Jeremy Marsden, Mario Santinami, Philippa Corrie, Steinar Aamdal, Paolo A Ascierto, Poulam M Patel, Wim H Kruit, Lars Bastholt, Lorenzo Borgognoni, Maria Grazia Bernengo, Neville Davidson, Larissa Polders, Michel Praet, Alan Spatz. 1. 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.
Abstract
PURPOSE: 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. PATIENTS AND 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. CONCLUSION:GM2-KLH/QS-21 vaccination does not improve outcome for patients with stage II melanoma.
RCT Entities:
PURPOSE: 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. PATIENTS AND 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. CONCLUSION:GM2-KLH/QS-21 vaccination does not improve outcome for patients with stage II melanoma.
Authors: Kelly M McMasters; Michael E Egger; Michael J Edwards; Merrick I Ross; Douglas S Reintgen; R Dirk Noyes; Robert C G Martin; James S Goydos; Peter D Beitsch; Marshall M Urist; Stephan Ariyan; Jeffrey J Sussman; B Scott Davidson; Jeffrey E Gershenwald; Lee J Hagendoorn; Arnold J Stromberg; Charles R Scoggins Journal: J Clin Oncol Date: 2016-02-08 Impact factor: 44.544
Authors: Irene Y Cheung; Nai-Kong V Cheung; Shakeel Modak; Audrey Mauguen; Yi Feng; Ellen Basu; Stephen S Roberts; Govind Ragupathi; Brian H Kushner Journal: J Clin Oncol Date: 2020-12-16 Impact factor: 44.544