Blood baseline neutrophil count predicts bevacizumab efficacy in glioblastoma.
Fiche publication
Date publication
octobre 2016
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BERTAUT Aurélie, Dr BOIDOT Romain, Pr GHIRINGHELLI François, Mme TRUNTZER Caroline, Dr VINCENT Julie, Dr DERANGERE Valentin
Tous les auteurs :
Bertaut A, Truntzer C, Madkouri R, Kaderbhai CG, Derangère V, Vincent J, Chauffert B, Aubriot-Lorton MH, Farah W, Mourier KL, Boidot R, Ghiringhelli F
Lien Pubmed
Résumé
Bevacizumab is used to treat glioblastoma; however, no current biomarker predicts its efficacy. We used an exploratory cohort of patients treated with the radiochemotherapy then bevacizumab or chemotherapy at recurrence (N = 265). Bevacizumab use increased median overall survival (OS) 18.7 vs 11.3 months, p = 0.0014). In multivariate analysis, age, initial surgery, neutrophil count, Karnofsky status >70% and bevacizumab administration were independent prognostic factors of survival. We found an interaction between bevacizumab use and baseline neutrophil count. The cut-off value for the neutrophil count was set at 6000/mm3. Only patients with a high neutrophil count benefited from the bevacizumab treatment (17.3 vs 8.8 months p < 0.0001). We validated this result using data from the TEMAVIR trial, which tested the efficacy of neoadjuvant bevacizumab plus irinotecan versus radiochemotherapy in the first-line treatment of glioblastoma. Transcriptomic data from TCGA underlined that CSF3 expression, the gene encoding G-CSF, the growth factor for neutrophils, correlated with VEGF-A-dependent angiogenesis. In another independent cohort (BELOB trial), which compared lomustine versus lomustine plus bevacizumab at recurrence, bevacizumab only benefited patients with high CSF3 expression in the tumor. These data suggest that only patients with a high peripheral neutrophil count before bevacizumab treatment benefited from this therapy.
Mots clés
bevacizumab, glioblastoma, prognosistic factor
Référence
Oncotarget. 2016 Oct;7(43):70948-70958