Patterns of Care and Outcomes of Patients With METAstatic Gastrointestinal Stromal Tumors (GIST) in a Real-life Setting: the METAGIST Observational Study
Conditions: Gastro Intestinal Stromal Tumor
Sponsor: Institut Bergonié

ID: IB2019-METAGIST     
 
Patterns of Care and Outcomes of Patients With METAstatic Gastrointestinal Stromal Tumors 
(METAGIST) 
    
 
NCT03963544 
Sept 1, 2018 
 
Title 
 
METAGIST 
Patterns of care and outcomes of patients with METAstatic GIST in a real-
life setting: the METAGIST national observational study from the GSF-GETO 
 
Rational 
Gastro intestinal stromal tumors (GIST) are rare mesenchymal tumors of the 
gastrointestinal tract characterized by somatic mutations in the gene encoding 
the KIT or the PDGFR alpha protein1. Treatment of localized forms relies on 
adequate surgery without tumor spillage and systemic treatment with imatinib 
according to risk of relapse defined by localization, tumor size and mitotic 
count, as well as mutational status. Advanced and relapsing forms are currently 
treated with oral tyrosine-kinase inhibitors (TKI) of KIT and PDGFR such as 
Imatinib, Sunitinib and Regorafenib2,3. Over two decades significant changes in 
drug discovery have impacted treatment strategies, notably via patient’s 
access to various clinical trials. The use of focal treatments such as surgery or 
interventional radiology with mini invasive procedure of oligometastasis is also 
being proposed in some cases.  
There is no precise data on patterns of sequential treatments used, especially 
proportions of patients with metastatic GIST eventually benefiting from access 
to a clinical trial or a focal treatment strategy in the course of their disease, and 
their results in terms of survival on a real life national level. 
Using the French sarcoma Group national database we aim at describing 
treatments strategies proposed patients with metastatic GIST in the real life 
setting. 
Objectives 
Primary objective 
To describe clinic-biological profiles, patterns of care and modalities of 
treatment of patients with metastatic GIST in a real-life national setting. 
 
Secondary objectives 
- 
time to next treatment (TNT)  
- 
 overall survival 
- 
proportion of patients included in a clinical trial during the course of 
their disease 
- 
 

Material 
and 
Methods 
 
Inclusion  
- 
patients ≥ 18 years old  
- 
with a diagnosis of metastatic GIST (metastatic at diagnostic or 
metastatic relapse) 
- 
From 1990 to 2018 
- 
with histological review performed by members of the pathological 
sub-committee of the GSF-GETO 
- 
treated in one of the participating national reference network centers 
members of the GSF-GETO  
- 
included in the prospectively maintained database of the GSF-GETO: 
the ConticaGIST 
 
Methods 
Descriptive data  (see SARCOMABCB DICTIONNARY) 
- 
Initial patients characteristics: age, gender, PS 
- 
tumor characteristics : date, histology, location, size, mitotic count, 
miettinien classification, mutational status 
- 
Initial treatment : initial surgery type, date, margins, tumor spillage, 
adjuvant systemic treatment (start and stop date) 
- 
Metastatic disease characteristics : date, PS, location of metastasis 
- 
Treatment in the metastatic setting : molecule used (start and stop 
date, best RECIST response), locoregional treatment performed, 
inclusion in a clinical trial 
- 
Latest status : date, patient lastest Status, tumor latest status 
 
Survival data  
- 
Time to next treatment (TNT) TNT defined as the time from the 
systemic treatment onset to the next treatment or death due to any 
cause, whichever came first. When neither death nor new systemic 
therapy is observed, TNT is censored at the date of last patient contact. 
- 
Overall survival in the metastatic setting (OS) defined as the interval 
between the diagnosis of metastatic disease or the first-line systemic 
therapy onset and the time of death. When death is not observed, OS 
is censored at the date of last patient contact. 
 
Statistics 
 
Statistical analysis of the baseline demographics and clinical outcomes will be 
based on all data available up to the cut-off date of December 31, 2018.  
Descriptive statistics will be used to show the distribution of variables in the 
population. Multivariate logistic regression models will be used to identify 
biological and clinical factors associated with the type of treatment received 
and with the probability of survival 5 years after the diagnosis of metastases. 
Follow-up times will be described as median values based on the inverse 
Kaplan–Meier estimator. 
Prognostic factors of TNT and OS will be identified using Cox proportional 
hazard models. The variables included in the univariate and multivariate 
analyses are the descriptive data. 

The correlation between TNT and OS will be evaluated at each of the four first-
lines of metastatic chemotherapy by a Spearman rank correlation coefficient 
and expressed as a value between 0 (no association) and 1 (perfect 
association). We will use a reviewed copula-based approach that introduces an 
iterative multiple imputation method for the estimation of the correlation 
coefficient. The data will be analyzed using the SAS v9.3 and R v3.3 software 
packages. 
Timeline 
 
February 2019 : end of collection of data and updating of the conticaGIST 
 
March - April 2019 : first version statistical analyses 
 
Ref 
1. 
Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in 
human gastrointestinal stromal tumors. Science. 1998;279(5350):577-580. 
2. 
Buchdunger E, Zimmermann J, Mett H, et al. Inhibition of the Abl protein-
tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. 
Cancer Res. 1996;56(1):100-104. 
3. 
Demetri GD, Reichardt P, Kang YK, et al. Efficacy and safety of regorafenib for 
advanced gastrointestinal stromal tumours after failure of imatinib and 
sunitinib (GRID): an international, multicentre, randomised, placebo-
controlled, phase 3 trial. Lancet. 2013;381(9863):295-302.