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

J Clin Oncol. 2013 Oct 20;31(30):3831-7. doi: 10.1200/JCO.2012.47.9303. Epub 2013 Sep 9.

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Cancer Vaccines / therapeutic use*
  • Disease-Free Survival
  • Female
  • G(M2) Ganglioside / therapeutic use*
  • Hemocyanins / therapeutic use*
  • Humans
  • Kaplan-Meier Estimate
  • Lymph Nodes / pathology
  • Lymph Nodes / surgery
  • Lymphatic Metastasis
  • Male
  • Melanoma / mortality
  • Melanoma / pathology*
  • Melanoma / prevention & control
  • Melanoma / surgery*
  • Middle Aged
  • Neoplasm Staging
  • Saponins / therapeutic use
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / prevention & control
  • Skin Neoplasms / surgery*
  • Watchful Waiting*

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Saponins
  • G(M2) Ganglioside
  • saponin QA-21V1
  • Hemocyanins
  • keyhole-limpet hemocyanin