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Treatment effects measured by restricted mean survival time in trials of immune checkpoint inhibitors for cancer.
Annals of Oncology ( IF 50.5 ) Pub Date : 2018-05-01 , DOI: 10.1093/annonc/mdy075
F Liang 1 , S Zhang 2 , Q Wang 3 , W Li 4
Affiliation  

Background The hazard ratio (HR) is used routinely to quantify the treatment effect for time-to-event end points in oncology trials, but its use requires that there be proportional hazards in the treatment arms. Non-proportional hazards are observed frequently in cancer immunotherapy trials due to the long-term survival and delayed clinical effect. Although values of HR are quoted in such trials, they are not valid measures of outcome. Methods Reports of parallel group randomized controlled trials (RCTs) evaluating immune checkpoint inhibitors with overall survival data were eligible. For each trial, the ratio of restricted mean survival time (RMST) between the arms was based on reconstructed individual patient data for overall survival. Results Twenty-five RCTs totaling 12 870 patients were included in this study. Overall survival was used as primary or coprimary end point in 18 trials (72%). In all trials, there was agreement between the ratio of RMST or RMTL and the reported HR about the direction of treatment effect. Estimates of HR provided larger estimates of treatment effect than the ratio of RMST or RMTL in all these trials. The estimated HR and RMST-based measures were in agreement regarding the statistical significance of the effect in all but two trials. Conclusions Ratio of RMST is a complementary technique that provides alternative method of summarizing treatment effects. Proportional hazards of the treatment effect should not be assumed in RCTs evaluating immune checkpoint inhibitors, and RMST analysis should be reported in such trials.

中文翻译:

在癌症免疫检查点抑制剂试验中,通过有限的平均生存时间来衡量治疗效果。

背景技术风险比(HR)通常用于量化肿瘤试验中从事件到终点的治疗效果,但要使用该风险比,要求治疗组中存在成比例的危害。由于长期生存和延迟的临床效果,在癌症免疫治疗试验中经常观察到非比例风险。尽管在此类试验中引用了HR的值,但它们不是有效的结局指标。方法平行组随机对照试验(RCT)评估免疫检查点抑制剂及总体生存数据的报告均符合条件。对于每个试验,两臂之间的受限平均生存时间(RMST)之比是基于重建的个体患者总体生存数据。结果本研究共纳入25项RCT,共12 870例患者。18项试验将总生存作为主要终点或辅助终点(72%)。在所有试验中,RMST或RMTL的比率与所报告的HR有关治疗效果的方向之间存在一致性。在所有这些试验中,HR估计值提供的治疗效果估计值均大于RMST或RMTL的比率。在除两项试验之外的所有试验中,基于HR和RMST的估计估算值均对该作用的统计学意义一致。结论RMST比率是一项补充技术,为总结治疗效果提供了另一种方法。在评估免疫检查点抑制剂的随机对照试验中,不应假定存在治疗效果的比例风险,并且在此类试验中应报告RMST分析。关于治疗效果的方向,RMST或RMTL的比率与所报告的HR之间存在一致性。在所有这些试验中,HR估计值提供的治疗效果估计值均大于RMST或RMTL的比率。在除两项试验之外的所有试验中,基于HR和RMST的估计估算值均对该作用的统计学意义一致。结论RMST比率是一项补充技术,为总结治疗效果提供了另一种方法。在评估免疫检查点抑制剂的随机对照试验中,不应假定存在治疗效果的比例风险,并且在此类试验中应报告RMST分析。关于治疗效果的方向,RMST或RMTL的比率与所报告的HR之间存在一致性。在所有这些试验中,HR估计值提供的治疗效果估计值均大于RMST或RMTL的比率。在除两项试验之外的所有试验中,基于HR和RMST的估计估算值均对该作用的统计学意义一致。结论RMST比率是一项补充技术,为总结治疗效果提供了另一种方法。在评估免疫检查点抑制剂的随机对照试验中,不应假定存在治疗效果的比例风险,并且在此类试验中应报告RMST分析。在除两项试验之外的所有试验中,基于HR和RMST的估计估算值均对该作用的统计学意义一致。结论RMST比率是一项补充技术,为总结治疗效果提供了另一种方法。在评估免疫检查点抑制剂的随机对照试验中,不应假定存在治疗效果的比例风险,并且在此类试验中应报告RMST分析。在除两项试验之外的所有试验中,基于HR和RMST的估计估算值均对该作用的统计学意义一致。结论RMST比率是一项补充技术,为总结治疗效果提供了另一种方法。在评估免疫检查点抑制剂的随机对照试验中,不应假定存在治疗效果的比例风险,并且在此类试验中应报告RMST分析。
更新日期:2018-02-23
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