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

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: Alexander M M Eggermont, 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 31 Issue 30 Pg. 3831-7 (Oct 20 2013) ISSN: 1527-7755 [Electronic] United States
• PMID: 24019551 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, surgery)
• Lymphatic Metastasis
• Male
• Melanoma (mortality, pathology, prevention & control, surgery)
• Middle Aged
• Neoplasm Staging
• Saponins (therapeutic use)
• Skin Neoplasms (mortality, pathology, prevention & control, surgery)
• Watchful Waiting