Veuillez lire l’article suivant : Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, et al. Lomustine and bevacizumab inprogressive glioblastoma. N Engl J Med 2017;377:1954-63.
Question 1 - Cochez la ou les réponse(s) exacte(s) :
Étude observationnelle correspond aux études épidémiologiques. Il s’agit ici d’une étude interventionnelle puisque randomisée avec administration d’un traitement.
Question 2 - Cochez la ou les réponse(s) exacte(s) :
“No standard of care has been established”
“Randomized trials involving patients with newly diagnosed glioblastoma showed no overall survival benefit from bevacizumab alone”
“This randomized phase 3 trial”
“At first progression of glioblastoma after standard chemoradiotherapy”
“At first progression of glioblastoma after standard chemoradiotherapy”
Question 3 - Cochez le ou les items correct(s) concernant le critère de jugement principal :
Objectif car ne nécessite pas d’interprétation : la mort.
Car directement en lien avec l’objectif recherché.
Il s’agit d’un critère censuré.
Question 4 - Quels sont les critères de jugements secondaires de cette étude ?
Critère de jugement principal.
“Secondary end points included progression free survival, land mark analyses for progression free and overall survival, toxic effects according to version 4.0 of the Common Terminology Criteria for Adverse Events, response rates according to the Response Assessment in NeuroOncology (RANO) criteria15 (see the Methods section in the Supplementary Appendix), neurologic deterioration–free survival (defined as the time from randomization to documentation of neurologic deterioration or death), clinical or neurologic deterioration–free survival, glucocorticoid use, health-related quality of life of both patients and health care proxies, the development of symptoms of neurocognitive deterioration, and assessments of predictive factors”.
Question 5 - Cochez la ou les réponse(s) exacte(s) :
“Patients were accepted into the trial after histologic confirmation of glioblastoma”
“Patients were excluded if they had undergone antiangiogenic treatment”
“The baseline evaluation included magnetic resonance imaging (MRI)”
“Complete blood count”
Question 6 - Quels items ont permis aux auteurs de calculer le nombre de sujets nécessaires ?
Risque alpha de 2,5 %
“We calculated that at least 327 overall survival events (deaths) would be required for the trial to have 80% power to detect a hazard ratio of 0.72 (rate of overall survival at 9 months of 51.7% in the combination group and 40% in the monotherapy group), on the basis of a one-sided logrank test at a significance level of 2.5%”.
Question 7 - Cochez la ou les réponse(s) exacte(s) :
“1 – puissance”
“At a significance level of 2.5%”
“Analyses were conducted on an intention to treat basis”
“The EORTC used four stratification criteria to centrally randomly assign patients”
“Four stratification criteria to centrally randomly assign patients”
Question 8 - Cochez la ou les réponse(s) exacte(s) :
“A total of 437 patients underwent randomization”
“A central neuroradiologic review was performed in 418 of 437 patients (95.7%)”
“Randomized treatment was started for 98.7% of the patients in the monotherapy group and 98.3% in the combination group”
“The main reason for discontinuing treatment was disease progression”
“Grade 3 to 5 adverse events occurred in 38.1% of the patients in the monotherapy group and in 63.6% of the patients in the combination group”
Question 9 - Cochez la ou les réponse(s) exacte(s) :
“With 329 overall survival events (75.3%), the combination treatment did not provide a survival advantage”
“Over a period of 37 months from November 2011 through December 2014”
“At 38 institutions in eight countries”
“Eight countries”
“The median progression free survival was 1.5 months (95% CI, 1.5 to 2.5) in the monotherapy group and 4.2 months (95 % CI, 3.7 to 4.3) in the combination group according to local assessments (hazard ratio for disease progression or death in the combination group, 0.49; 95% CI, 0.39 to 0,61; P < 0,001) (fig. 2B)”
Question 10 - Concernant le tableau 1 de l'article, cochez la ou les réponse(s) exacte(s) :
16 patients
59,8 ans
Les tests statistiques ne sont pas réalisés dans les tableaux 1 des essais cliniques de phase III car il s’agit des caractéristiques initiales des populations incluses avant l’intervention thérapeutique. Le lecteur doit donc juger de la répartition des groupes par lui-même. Ici, la proportion est un peu plus importante (39,6 % vs 38,9 %) mais probablement sans conséquences sur les résultats.
Question 11 - Concernant la figure 1 de l'article, cochez la ou les réponse(s) exacte(s) :
5 dans un groupe et 2 dans l’autre
C’est la définition, et le flow chart nous le confirme.
264 + 144
Question 12 - Concernant la figure 2 de l'article, cochez la ou les réponse(s) exacte(s) :
“Overall survival and progression-free survival in the intention-to-treat population”
Droite passant par l’ordonnée 0,5.
Au nombre de patients n’ayant pas encore présenté l’événement et non perdus de vue.
Question 13 - Cochez la ou les réponse(s) exacte(s) :
“Glucocorticoid use was equally distributed between the two groups”
“No significant difference in the time before starting glucocorticoids was observed between the combination group (median, 8.3 months; 95% CI, 6.8 to not reached) and the monotherapy group (median, 8.6 months; 95% CI, 4.5 to 12.7) (P=0.33)”
“In the combination group, five deaths were noted (two from myocardial infarction and one each from large intestine perforation, sepsis, and intracranial hemorrhage)”
“In the combination group, five deaths were noted (two from myocardial infarction and one each from large intestine perforation, sepsis, and intracranial hemorrhage)”
“One patient in the monotherapy group died from a lung infection that was unrelated to the tumor”
Question 14 - Cochez la ou les réponse(s) exacte(s) :
“Adding bevacizumab to lomustine did not confer a survival advantage over lomustine”
“The addition of bevacizumab in the current trial did not result in reduced use of glucocorticoids”
“MGMT status was not predictive of efficacy outcomes with the combination treatment”
“The effect on progression free survival was not associated with an increase in overall survival, and combination therapy was associated with increased toxicity”
“Although earlier reports from the BRAIN trial (involving patients with recurrent glioblastoma)1 and from the Avastin in Glioblastoma trial (involving patients with newly diagnosed glioblastoma)8 suggested that bevacizumab had glucocorticoidsparing effects, the addition of bevacizumab in the current trial did not result in reduced use of glucocorticoids”
Question 15 - Cochez la ou les réponse(s) exacte(s) : il s’agit d’une étude de :
Étude randomisée contrôlée de bonne puissance : grade A de niveau 1 de la Haute Autorité de santé.
