Hersey Peter, Coates Alan S, McCarthy William H, Thompson John F, Sillar Robert W, McLeod Roderick, Gill P Grantley, Coventry Brendon J, McMullen Amanda, Dillon Haryana, Simes R John
Sydney Melanoma Unit, University of Sydney and Royal Prince Alfred Hospital, and the Cancer Council Australia, Sydney.
J Clin Oncol. 2002 Oct 15;20(20):4181-90. doi: 10.1200/JCO.2002.12.094.
Patients with high-risk melanoma treated by immunotherapy with vaccinia viral lysates were found in phase II studies to have improved survival compared with historical controls. We therefore elected to test this therapy in a phase III study.
A prospective, randomized, multicenter trial to determine whether immunotherapy with a vaccine prepared from vaccinia melanoma cell lysates (VMCL) over a 2-year period after definitive surgery would improve relapse-free survival (RFS) and overall survival (OS) in patients with American Joint Committee on Cancer stage IIB and III melanoma compared with a control group treated only with surgery.
A total of 700 patients were randomized: 353 to VMCL and 347 to no immunotherapy. Seventy-seven percent had lymph node (LN) metastases and 66% had clinically detected LN metastases. Analysis on the basis of all eligible, randomized patients (n = 675) found, after a median follow-up period of 8 years, a median OS of 88 months in the control versus 151 months in the treated group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.64 to 1.02; P =.068 by stratified univariate Cox analysis). At 5 and 10 years, survival rates for control and treated patients were 54.8% v 60.6% and 41% v 53.4%, respectively. Median RFS was 43 months in the control group compared with 83 months in the treated group (HR, 0.86; 95% CI, 0.7 to 1.07; P =.17). RFS at 5 years was 50.9% for the treated group and 46.8% for the control group. There were no selective benefits from the vaccine for particular subsets of patients.
Immunotherapy with VMCL was not associated with a statistically significant improvement in OS or RFS, with CIs not ruling out important gains from such treatment.
在II期研究中发现，接受牛痘病毒裂解物免疫治疗的高危黑色素瘤患者与历史对照相比，生存率有所提高。因此，我们选择在III期研究中测试这种疗法。
一项前瞻性、随机、多中心试验，旨在确定在根治性手术后的2年期间，使用由牛痘黑色素瘤细胞裂解物（VMCL）制备的疫苗进行免疫治疗，与仅接受手术治疗的对照组相比，是否能提高美国癌症联合委员会IIB期和III期黑色素瘤患者的无复发生存期（RFS）和总生存期（OS）。
共有700例患者被随机分组：353例接受VMCL治疗，347例不接受免疫治疗。77%的患者有淋巴结（LN）转移，66%的患者有临床检测到的LN转移。基于所有符合条件的随机分组患者（n = 675）进行分析，在中位随访期8年后，对照组的中位OS为88个月，治疗组为151个月（风险比[HR]，0.81；95%置信区间[CI]，0.64至1.02；分层单变量Cox分析P = 0.068）。在5年和10年时，对照组和治疗组患者的生存率分别为54.8%对60.6%和41%对53.4%。对照组的中位RFS为43个月，治疗组为83个月（HR，0.86；95%CI，0.7至1.07；P = 0.17）。治疗组5年时的RFS为50.9%，对照组为46.8%。该疫苗对特定亚组患者没有选择性益处。
VMCL免疫治疗与OS或RFS的统计学显著改善无关，置信区间不排除这种治疗有重要获益。
