9004 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 were: 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 were 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. The IDMC recommended trial 18961 to be stopped and vaccinations to be halted in pts still receiving VAC. Pts should continue to be followed for the trial’s endpoints. Conclusions: Adjuvant GM2-KLH21 vaccination is ineffective and could even be detrimental in stage II melanoma patients. RFS DMFS OS Obs. GM2-KLH21 Obs. GM2-KLH21 Obs. GM2-KLH21 Nb. Events 132 135 65 86 35 56 2-yr % (SE%) 77.8% (1.9%) 75.1% (2.0%) 88.5 (1.6%) 82.4 (1.9%) 92.4 (1.4%) 89.2 (1.7%) HR (CI)(1) 1.02 (0.77-1.36)* 1.33 (0.77-2.28)** 1.57 (0.68-3.64)*** p- value(1) 0.85 0.08 0.03 HR (CI)(2) 1.00 (0.75-1.34)* 1.32 (0.76- 2.30)** 1.66 (0.66-3.99)*** p-value(2) 0.99 0.10 0.02 HR = Hazard Ratio; * 98% CI, ** 99.9% CI, *** 99.99% CI. (1) Cox model, unadjusted for stratification factors; (2) Cox model, stratified for stratification factors No significant financial relationships to disclose.
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Eggermont et al. (2008) studied this question.