EORTC 18961: Post-operative adjuvant ganglioside GM2-KLH21 vaccination treatment vs observation in stage II (T3-T4N0M0) melanoma: 2nd interim analysis led to an early disclosure of the results.

• Abstract No: 9004
• Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 9004)
• Author(s): A. M. Eggermont, S. Suciu, W. Ruka, J. Marsden, A. Testori, P. Corrie, S. Aamdal, P. A. Ascierto, P. Patel, A. Spatz, EORTC Melanoma Group

Abstract
Background: EORTC 18961 assessed in the largest adjuvant phase III trial to date in stage II melanoma the efficacy and toxicity of Ganglioside GM2-KLH21 Vaccination (VAC) Treatment vs Observation (OBS).

Methods
Patients (Pts)\ were observed or received vaccine sc once weekly week 1-4, every 3 months from week 12 for first 2 years and every 6 months during third year (total of 14 vaccinations).

Stratification Factors for Randomization
Breslow thickness, ulceration, being staged yes vs no by Sentinel Node (SNLD) or Elective Lymph Node Dissection (ELND), sex and institution.

Relapse-free survival (RFS) was the primary endpoint; Distant metastasis-free survival (DMFS) and overall survival (OS) were the prespecified secondary endpoints.

Intent-to-treat analysis was performed.

Results

• Between March 2002 and Dec. 2005, 1,314 pts entered the trial.
• Patient demographics showed perfect balance for prognostic factors.
  
• The 2nd interim analysis was performed when 267 RFS events were reported, i.e. 67% of the total number required at final analysis.
  
• Median follow-up was 1.8 years.
  

Similar Treatment Differences

• Obtained in lympnhnode-staged (N=644) or non-staged (N=670) patients.
• Grade 3 - toxicities occurred in < 2%.(VAC) and in < 1% (OBS).
• Grade 2 - toxicities comprised fatigue (15% vs 3%), fever (9% vs 1%), nausea (3% vs 1%).
  
• Local grade 3 - toxicity occurred in 4 % (VAC).
  
• The EORTC IDMC reviewed both safety and efficacy data.
  
• For the primary endpoint, RFS, the criteria for stopping for futility were met. 
• For DMFS and OS, the results pointed in the direction of a detrimental effect of the vaccine.
  

Conclusions
Adjuvant GM2-KLH21 vaccination is ineffective and could even be detrimental in stage II melanoma patients.