Oncotarget

Meta-Analysis:

Surrogate endpoints in advanced sarcoma trials: 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 and Carine Bellera _

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Oncotarget. 2018; 9:34617-34627. https://doi.org/10.18632/oncotarget.26166

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Abstract

Marion Savina1,2,3,4, Saskia Litière5, Antoine Italiano6, Tomasz Burzykowski7, Franck Bonnetain8, Sophie Gourgou9, Virginie Rondeau3,10, Jean-Yves Blay11,12, Sophie Cousin6, Florence Duffaud13, Hans Gelderblom14, Alessandro Gronchi15, Ian Judson16, Axel Le Cesne17, Paul Lorigan18, Joan Maurel19, Winette van der Graaf20,21,23, Jaap Verweij22, Simone Mathoulin-Pélissier1,2,3,4 and Carine Bellera1,2,3,4

1Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, Bordeaux cedex 33076, France

2INSERM CIC-EC 14.01 (Clinical Epidemiology), Bordeaux 33000, France

3INSERM, ISPED, Centre INSERM U1219 Bordeaux Population Health Center, Epicene Team, Bordeaux 33000, France

4University of Bordeaux, ISPED, Centre INSER M U1219 Bordeaux Population Health, Epicene Team, Bordeaux 33000, France

5European Organisation for Research and Treatment of Cancer (EORTC), Brussels 1200, Belgium

6Medical Oncology Unit, Institut Bergonié, Comprehensive Cancer Center, Bordeaux cedex 33076, France

7Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BioStat), Hasselt University, Hasselt 3500, Belgium

8Methodology and Quality of life in Oncology Unit, Besançon EA3181, France

9Biometrics Unit, Institut du Cancer de Montpellier, Univ. Montpellier, Montpellier 34298, France

10INSERM, ISPED, Centre INSERM U1219 Bordeaux Population Health Center, Biostatistic Team, Bordeaux 33000, France

11Centre Léon Bérard, Comprehensive Cancer Center, Lyon 69008, France

12University Claude Bernard Lyon I, Lyon 69000, France

13Medical Oncology Unit, University Hospital La Timone and University of Aix-Marseille, Marseille 13005, France

14Department of Medical Oncology, Leiden University Medical Center, Leiden 2300RC, The Netherlands

15Sarcoma Service, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

16Institute of Cancer Research, Sutton, Surrey, United Kingdom

17Medicine Department, Institut Gustave Roussy, Comprehensive Cancer Center, Villejuif 94800, France

18University of Manchester and Christie NHS Foundation Trust, Manchester M20 4BX, UK

19Department of Medical Oncology, Hospital Clinic, CIBERehd, Translational Genomics and Targeted Therapeutics in Solid Tumors (IDIBAPS), Barcelona 08036, Spain

20The Institute of Cancer Research, Sutton, London SM2 5NG, United Kingdom

21Radboud University Medical Centre, Department of Medical Oncology, GA Nijmegen 6525, The Netherlands

22Department of Medical Oncology, Erasmus University Medical Center, CE Rotterdam 3015, The Netherlands

23Royal Marsden NHS Foundation Trust, Chelsea, London, United Kingdom

Correspondence to:

Carine Bellera, email: C.Bellera@bordeaux.unicancer.fr

Keywords: sarcoma; surrogate endpoints; meta-analysis; randomized trial; survival

Received: August 20, 2018     Accepted: September 13, 2018     Published: October 02, 2018

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.


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PII: 26166