High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: Results of Intergroup trial E1694/S9512/C509801
High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: Results of Intergroup trial E1694/S9512/C509801
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DOI：
10.1200/jco.2001.19.9.2370
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发表时间：
2001-05-01
影响因子：
45.3
通讯作者：
Rao, U
中科院分区：
文献类型：
--
作者：
Kirkwood, JM;Ibrahim, JG;Rao, U
目的：高剂量干扰素α-2b疗法（HDI）是目前高危黑色素瘤的标准辅助疗法，由于HDI相关的毒性，疫苗替代疗法备受关注。GM 2神经节苷脂是一种定义明确的黑色素瘤抗原，抗GM 2抗体与改善预后相关。我们进行了一项前瞻性、随机、组间试验，以评估HDI 1年与接种与钥孔血蓝蛋白缀合的GM 2并施用Q5-21（GMK）96周（每周x 4然后每12周x 8）的疗效。患者按性别和阳性淋巴结数量分层。主要终点是无复发生存期（RFS）和总生存期（OS）。结果：880例患者被随机分组（每个治疗组440例）; 774例患者符合疗效分析。在中期分析表明GMK劣于HDI后，试验关闭。对于符合条件的患者，HDI为GMK提供了统计学显著的RFS获益（风险比[HR] = 1.47，P = 0.0015）和OS获益（HR = 1.52，P = 0.009）。在意向治疗分析中观察到类似获益[RFS HR = 1.49; OS HR = 1.38）。HDI与0至大于或等于4个阳性淋巴结的所有患者亚组的治疗获益相关，但在淋巴结阴性亚组中观察到最大获益（RFS HR = 2.07; OS HR = 2.71 [合格人群））。在第29、85、365和720天对GM 2的抗体应答（即滴度大于或等于1：80）与RFS和OS改善的趋势相关（第29天P-2 = 0.068）。结论：本试验证明了HDI与GMK相比在复发风险高的黑色素瘤患者的RFS和OS方面具有显著的治疗益处。J Clin Oncol 19：2370-2380. (C)2001年，美国临床肿瘤学会。
Purpose: Vaccine alternatives to high-dose interferon alfa-2b therapy (HDI), the current standard adjuvant therapy for high-risk melanoma, are of interest because of toxicity associated with HDI. The GM2 ganglioside is a well-defined melanoma antigen, and anti-GM2 antibodies have been associated with improved prognosis. We conducted a prospective, randomized, intergroup trial to evaluate the efficacy of HDI for 1 year versus vaccination with GM2 conjugated to keyhole limpet hemocyanin and administered with Q5-21 (GMK) for 96 weeks (weekly x 4 then every 12 weeks x 8).Patients and Methods: Eligible patients had resected stage IIB/III melanoma. patients were stratified by sex and number of positive nodes. Primary end points were relapse-free survival (RFS) and overall survival (OS).Results: Eight hundred eighty patients were randomized (440 per treatment group); 774 patients were eligible for efficacy analysis. The trial was closed after interim analysis indicated inferiority of GMK compared with HDI. For eligible patients, HDI provided a statistically significant RFS benefit (hazard ratio [HR] = 1.47, P = .0015) and OS benefit (HR = 1.52, P = .009) for GMK versus HDI. Similar benefit was observed in the intent-to-treat analysis [RFS HR = 1.49; OS HR = 1.38). HDI was associated with a treatment benefit in all subsets of patients with zero to greater than or equal to four positive nodes, but the greatest benefit was observed in the node-negative subset (RFS HR = 2.07; OS HR = 2.71 [eligible population)). Antibody responses to GM2 (ie, titers greater than or equal to 1:80) at days 29, 85, 365, and 720 were associated with a trend toward improved RFS and OS (P-2 = .068 at day 29).Conclusion: This trial demonstrated a significant treatment benefit of HDI versus GMK in terms of RFS and OS in melanoma patients at high risk of recurrence. J Clin Oncol 19:2370-2380. (C) 2001 by American Society of Clinical Oncology.