The use of GM2-KLH/QS-21 vaccination in stage II melanoma patients did not improve outcomes, according to the results of the EORTC 18961 phase III trial.
The use of GM2-KLH/QS-21 vaccination in stage II melanoma patients did not improve outcomes, according to the results of the EORTC 18961 phase III trial published online in the Journal of Clinical Oncology.
Alexander M. M. Eggermont, MD, PhD, of Gustave Roussy Comprehensive Cancer Center, and colleagues had previously presented results of the interim analysis at ASCO 2008, and final results at ASCO 2010.
The study looked at the use of the GM2-KLH/QS-21 vaccine, which induces high immunoglobulin M and immunoglobulin G antibody responses, in 1,314 patients with a primary melanoma of 1.5 mm in thickness. The patients were randomly assigned to vaccination (n = 657) or observation (n = 657) and outcomes were compared for distant metastasis-free survival and overall survival.
At the second interim analysis in March 2007, after a median follow-up of 1.8 years, the trial was stopped for futility. No difference in recurrence-free survival was seen (HR = 1.00) and a detrimental effect on overall survival was seen (HR = 1.66; P = .02).
“At the final analysis, performed at a median follow-up of 4.2 years, no significant difference between vaccination and observation was observed for any efficacy endpoint, but overall survival from time of random assignment was reduced, as was survival after relapse,” the researchers wrote.
Patients assigned to the vaccine had a decreased recurrence-free survival of 1.2% (HR = 1.03; 95% CI, 0.84–1.25) and a decreased overall survival rate of 2.1% (HR = 1.16; 95% CI, 0.90–1.51).
Three percent of patients assigned to the vaccine experienced grade 3 to 4 adverse events compared with less than 1% of patients undergoing observation.
In their discussion of the study results, the researchers wrote that they cannot rule out that the use of this vaccine may have had a detrimental effect.
“It is striking that the ECOG (Eastern Cooperative Oncology Group) 1694 trial comparing the GM2-KLH/QS-21 vaccine with high-dose interferon (IFN), conducted in patients with stage IIb/III melanoma, was also stopped at the second interim analysis because of significantly inferior outcomes with the vaccination versus high-dose IFN regarding RFS and OS,” the researchers wrote. “The EORTC 18961 trial results lead to questions about the interpretation of the ECOG 1694 trial, specifically as regards the OS outcome being considered the result of the positive impact of high-dose IFN only and the rejection of the suggestion that vaccination was not deleterious in patient OS.”