Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials
Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials
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DOI：
10.1200/jco.2007.12.7837
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发表时间：
2008-02-01
影响因子：
45.3
通讯作者：
Kirkwood, John M.
中科院分区：
文献类型：
--
作者：
Korn, Edward L.;Liu, Ping-Yu;Kirkwood, John M.
目的
在转移性黑色素瘤的II期试验中观察到的客观肿瘤缓解率，从历史上看，并不能可靠地预示有意义的生存获益。为了促进将总生存期（OS）或无进展生存期（PFS）用作未来II期试验的终点，我们评估了合作组II期试验的历史数据，试图为OS和PFS制定基准，作为未来II期试验的参考点。
患者与方法
获取了1975年至2005年期间完成入组的42项II期试验（70个试验组）中患者的个体水平和试验水平数据，这些试验由西南肿瘤学组、东部肿瘤合作组、癌症与白血病B组、中北部癌症治疗组以及加拿大国家癌症研究所临床试验组开展。进行了单变量和多变量分析以确定预后变量，并检查了1年OS率和6个月PFS率在试验（组）间的变异性。
结果
在对OS进行的多变量生存分析中发现的具有统计学意义的个体水平和试验水平的预后因素包括体能状态、是否存在内脏疾病、性别以及试验是否排除脑转移患者。体能状态、性别和年龄是PFS具有统计学意义的预后因素。控制这些预后变量基本上消除了1年OS率在试验间的变异性，但没有消除6个月PFS率的试验间变异性。
结论
提供了利用II期试验中患者预后因素分布的1年OS或OS曲线的基准。提供了6个月PFS的类似基准，但由于该终点存在剩余的试验间变异，其使用更具问题。
PurposeObjective tumor response rates observed in phase II trials for metastatic melanoma have historically not provided a reliable indicator of meaningful survival benefits. To facilitate using overall survival ( OS) or progression-free survival ( PFS) as an endpoint for future phase II trials, we evaluated historical data from cooperative group phase II trials to attempt to develop benchmarks for OS and PFS as reference points for future phase II trials.Patients and MethodsIndividual-level and trial-level data were obtained for patients enrolled onto 42 phase II trials ( 70 trial arms) that completed accrual in the years 1975 through 2005 and conducted by Southwest Oncology Group, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, North Central Cancer Treatment Group, and the Clinical Trials Group of the National Cancer Institute of Canada. Univariate and multivariate analyses were performed to identify prognostic variables, and between-trial(-arm) variability in 1-year OS rates and 6-month PFS rates were examined.ResultsStatistically significant individual-level and trial-level prognostic factors found in a multivariate survival analysis for OS were performance status, presence of visceral disease, sex, and whether the trial excluded patients with brain metastases. Performance status, sex, and age were statistically significant prognostic factors for PFS. Controlling for these prognostic variables essentially eliminated between-trial variability in 1-year OS rates but not in 6-month PFS rates.ConclusionBenchmarks are provided for 1-year OS or OS curves that make use of the distribution of prognostic factors of the patients in the phase II trial. A similar benchmark for 6-month PFS is provided, but its use is more problematic because of residual between-trial variation in this endpoint.