Surrogate endpoints in advanced sarcoma trials: a meta-analysis.
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Date
2018-10-02ICR Author
Author
Savina, M
Litière, S
Italiano, A
Burzykowski, T
Bonnetain, F
Gourgou, S
Rondeau, V
Blay, J-Y
Cousin, S
Duffaud, F
Gelderblom, H
Gronchi, A
Judson, I
Le Cesne, A
Lorigan, P
Maurel, J
van der Graaf, W
Verweij, J
Mathoulin-Pélissier, S
Bellera, C
Type
Journal Article
Metadata
Show full item recordAbstract
Background 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).Results A total of 21 trials originally met the selection criteria and 14 RCTs ( N = 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.Materials and methods 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.Conclusions Our results do not support strong surrogate properties of PFS, TTP and TTF for OS in advanced STS.
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Research team
Sarcoma Clinical Trials
Language
eng
Date accepted
2018-09-13
License start date
2018-10-02
Citation
Oncotarget, 2018, 9 (77), pp. 34617 - 34627