Format

Send to

Choose Destination
Oncotarget. 2018 Oct 2;9(77):34617-34627. doi: 10.18632/oncotarget.26166. eCollection 2018 Oct 2.

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

Author information

1
Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, Bordeaux cedex 33076, France.
2
INSERM CIC-EC 14.01 (Clinical Epidemiology), Bordeaux 33000, France.
3
INSERM, ISPED, Centre INSERM U1219 Bordeaux Population Health Center, Epicene Team, Bordeaux 33000, France.
4
University of Bordeaux, ISPED, Centre INSER M U1219 Bordeaux Population Health, Epicene Team, Bordeaux 33000, France.
5
European Organisation for Research and Treatment of Cancer (EORTC), Brussels 1200, Belgium.
6
Medical Oncology Unit, Institut Bergonié, Comprehensive Cancer Center, Bordeaux cedex 33076, France.
7
Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BioStat), Hasselt University, Hasselt 3500, Belgium.
8
Methodology and Quality of life in Oncology Unit, Besançon EA3181, France.
9
Biometrics Unit, Institut du Cancer de Montpellier, Univ. Montpellier, Montpellier 34298, France.
10
INSERM, ISPED, Centre INSERM U1219 Bordeaux Population Health Center, Biostatistic Team, Bordeaux 33000, France.
11
Centre Léon Bérard, Comprehensive Cancer Center, Lyon 69008, France.
12
University Claude Bernard Lyon I, Lyon 69000, France.
13
Medical Oncology Unit, University Hospital La Timone and University of Aix-Marseille, Marseille 13005, France.
14
Department of Medical Oncology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
15
Sarcoma Service, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
16
Institute of Cancer Research, Sutton, Surrey, United Kingdom.
17
Medicine Department, Institut Gustave Roussy, Comprehensive Cancer Center, Villejuif 94800, France.
18
University of Manchester and Christie NHS Foundation Trust, Manchester M20 4BX, UK.
19
Department of Medical Oncology, Hospital Clinic, CIBERehd, Translational Genomics and Targeted Therapeutics in Solid Tumors (IDIBAPS), Barcelona 08036, Spain.
20
The Institute of Cancer Research, Sutton, London SM2 5NG, United Kingdom.
21
Radboud University Medical Centre, Department of Medical Oncology, GA Nijmegen 6525, The Netherlands.
22
Royal Marsden NHS Foundation Trust, Chelsea, London, United Kingdom.
23
Department of Medical Oncology, Erasmus University Medical Center, CE Rotterdam 3015, The Netherlands.

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:

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

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center