Surrogate endpoints in advanced sarcoma trials: a meta-analysis: a meta-analysis

Marion Savina; Saskia Litière; Antoine Italiano; Tomasz Burzykowski; Franck Bonnetain; Sophie Gourgou; Virginie Rondeau; Jean-Yves Blay; Sophie Cousin; Florence Duffaud; Hans Gelderblom; Alessandro Gronchi; Ian Judson; Axel Le Cesne; Paul Lorigan; Joan Maurel; Winette van der Graaf; Jaap Verweij; Simone Mathoulin-Pélissier; Carine Bellera

doi:10.18632/oncotarget.26166

Surrogate endpoints in advanced sarcoma trials: a meta-analysis: a meta-analysis

Marion Savina, Saskia Litière, Antoine Italiano, Tomasz Burzykowski, Franck Bonnetain, Sophie Gourgou, Virginie Rondeau, Jean-Yves Blay, Sophie Cousin, Florence Duffaud, Hans Gelderblom, Alessandro Gronchi, Ian Judson, Axel Le Cesne, Paul Lorigan, Joan Maurel, Winette van der Graaf, Jaap Verweij, Simone Mathoulin-Pélissier, Carine Bellera

Division of Cancer Sciences (L5)

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	PMID: 30349653
Pages (from-to)	34617-34627
Number of pages	11
Journal	Oncotarget
Volume	9
Issue number	77
DOIs	https://doi.org/10.18632/oncotarget.26166
Publication status	Published - 2 Oct 2018

Keywords

sarcoma, surrogate endpoints, meta-analysis, randomized trial, survival

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.26166

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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. (2018). Surrogate endpoints in advanced sarcoma trials: a meta-analysis: a meta-analysis. Oncotarget, 9(77), 34617-34627. Article PMID: 30349653 . https://doi.org/10.18632/oncotarget.26166

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abstract = "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.",

keywords = "sarcoma, surrogate endpoints, meta-analysis, randomized trial, survival",

author = "Marion Savina and Saskia Liti{\`e}re and Antoine Italiano and Tomasz Burzykowski and Franck Bonnetain and Sophie Gourgou and Virginie Rondeau and Jean-Yves Blay and Sophie Cousin and Florence Duffaud and Hans Gelderblom and Alessandro Gronchi and Ian Judson and {Le Cesne}, Axel and Paul Lorigan and Joan Maurel and {van der Graaf}, Winette and Jaap Verweij and Simone Mathoulin-P{\'e}lissier and Carine Bellera",

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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 2018, 'Surrogate endpoints in advanced sarcoma trials: a meta-analysis: a meta-analysis', Oncotarget, vol. 9, no. 77, PMID: 30349653 , pp. 34617-34627. https://doi.org/10.18632/oncotarget.26166

TY - JOUR

T1 - Surrogate endpoints in advanced sarcoma trials: a meta-analysis

T2 - a meta-analysis

AU - Savina, Marion

AU - Litière, Saskia

AU - Italiano, Antoine

AU - Burzykowski, Tomasz

AU - Bonnetain, Franck

AU - Gourgou, Sophie

AU - Rondeau, Virginie

AU - Blay, Jean-Yves

AU - Cousin, Sophie

AU - Duffaud, Florence

AU - Gelderblom, Hans

AU - Gronchi, Alessandro

AU - Judson, Ian

AU - Le Cesne, Axel

AU - Lorigan, Paul

AU - Maurel, Joan

AU - van der Graaf, Winette

AU - Verweij, Jaap

AU - Mathoulin-Pélissier, Simone

AU - Bellera, Carine

PY - 2018/10/2

Y1 - 2018/10/2

N2 - 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.

AB - 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.

KW - sarcoma, surrogate endpoints, meta-analysis, randomized trial, survival

U2 - 10.18632/oncotarget.26166

DO - 10.18632/oncotarget.26166

M3 - Article

C2 - 30349653

SN - 1949-2553

VL - 9

SP - 34617

EP - 34627

JO - Oncotarget

JF - Oncotarget

IS - 77

M1 - PMID: 30349653

ER -

Surrogate endpoints in advanced sarcoma trials: a meta-analysis: a meta-analysis

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

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