接种疫苗未能改善黑素瘤患者的预后
接种疫苗未能改善黑素瘤患者的预后。发表于J Clinical Oncology的一篇文章表明，接种GM2/KLH-QS-21疫苗对II期黑色素瘤患者没有益处。
接种GM2/KLH-QS-21可以刺激产生抗GM2神经节苷脂的抗体。GM2神经节苷脂，是一种在大多数黑色素瘤表达的抗原，但在正常组织中的表达有限，因此被认为是一个合适的治疗靶抗原。对GM2的血清学应答是黑色素瘤患者的积极预后因素之一。
来自法国的研究人员筛选了1314例II期黑色素瘤（原发性黑色素瘤厚度大于1.5毫米，T3-4N0M0 ; AJCC第二阶段）患者，随机分成两组。试验组接种GM2-KLH-QS21疫苗，第一个月每周皮下注射一次，然后每三个月一次持续两年，第三年每半年进行一次。
实验在1.8年左右由于患者被注射手臂部位的不良反应而终止，最后随访中位数时间为4.2年。共有400例复发，236例死亡，其中9例死亡是未复发患者。未复发的生存率和总的生存率分别下降了1.2％和2.1％。
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
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.
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.
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.
GM2-KLH/QS-21 vaccination does not improve outcome for patients with stage II melanoma.
接种GM2/KLH-QS-21可以刺激产生抗GM2神经节苷脂的抗体。GM2神经节苷脂，是一种在大多数黑色素瘤表达的抗原，但在正常组织中的表达有限，因此被认为是一个合适的治疗靶抗原。对GM2的血清学应答是黑色素瘤患者的积极预后因素之一。
来自法国的研究人员筛选了1314例II期黑色素瘤（原发性黑色素瘤厚度大于1.5毫米，T3-4N0M0 ; AJCC第二阶段）患者，随机分成两组。试验组接种GM2-KLH-QS21疫苗，第一个月每周皮下注射一次，然后每三个月一次持续两年，第三年每半年进行一次。
实验在1.8年左右由于患者被注射手臂部位的不良反应而终止，最后随访中位数时间为4.2年。共有400例复发，236例死亡，其中9例死亡是未复发患者。未复发的生存率和总的生存率分别下降了1.2％和2.1％。
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
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.
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