Savina Marion, Litière Saskia, Italiano Antoine, Burzykowski Tomasz, Bonnetain Franck, Gourgou Sophie, Rondeau Virginie, Blay Jean-Yves, Cousin Sophie, Duffaud Florence, Gelderblom Hans, Gronchi Alessandro, Judson Ian, Le Cesne Axel, Lorigan Paul, Maurel Joan, van der Graaf Winette, Verweij Jaap, Mathoulin-Pélissier Simone, Bellera Carine
Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, Bordeaux cedex 33076, France.
INSERM CIC-EC 14.01 (Clinical Epidemiology), Bordeaux 33000, France.
Oncotarget. 2018 Oct 2;9(77):34617-34627. doi: 10.18632/oncotarget.26166.
Alternative endpoints to overall survival (OS) are frequently used to assess treatment efficacy in randomized controlled trials (RCT). Their properties in terms of surrogate outcomes for OS need to be assessed. We evaluated the surrogate properties of progression-free survival (PFS), time-to-progression (TTP) and time-to-treatment failure (TTF) in advanced soft tissue sarcomas (STS).
A total of 21 trials originally met the selection criteria and 14 RCTs ( = 2846) were included in the analysis. Individual-level associations were moderate (highest for 12-month PFS: Spearman's rho = 0.66; 95% CI [0.63; 0.68]). Trial-level associations were ranked as low for the three endpoints as per the IQWiG criterion.
We performed a meta-analysis using individual-patient data (IPD). Phase II/III RCTs evaluating therapies for adults with advanced STS were eligible. We estimated the individual- and the trial-level associations between then candidate surrogates and OS. Statistical methods included weighted linear regression and the two-stage model introduced by Buyse and Burzykowski. The strength of the trial-level association was ranked according to the German Institute for Quality and Efficiency in Health Care (IQWiG) guidelines.
Our results do not support strong surrogate properties of PFS, TTP and TTF for OS in advanced STS.
在随机对照试验（RCT）中，总生存期（OS）的替代终点常被用于评估治疗效果。需要评估它们作为OS替代结局的特性。我们评估了晚期软组织肉瘤（STS）中无进展生存期（PFS）、疾病进展时间（TTP）和治疗失败时间（TTF）的替代特性。
共有21项试验最初符合入选标准，14项RCT（n = 2846）纳入分析。个体水平的相关性为中等（12个月PFS最高：Spearman相关系数ρ = 0.66；95%CI[0.63；0.68]）。根据IQWiG标准，三项终点在试验水平的相关性均被列为低。
我们使用个体患者数据（IPD）进行了一项荟萃分析。评估晚期STS成人患者治疗的II/III期RCT符合条件。我们估计了候选替代指标与OS之间的个体水平和试验水平的相关性。统计方法包括加权线性回归以及Buyse和Burzykowski提出的两阶段模型。试验水平相关性的强度根据德国卫生保健质量与效率研究所（IQWiG）指南进行排名。
我们的结果不支持PFS、TTP和TTF在晚期STS中作为OS的强替代特性。
