Blood baseline neutrophil count predicts bevacizumab efficacy in glioblastoma

• Published in: Oncotarget Vol. 7; no. 43; pp. 70948 - 70958
• Main Authors: Bertaut, Aurélie, Truntzer, Caroline, Madkouri, Rachid, Kaderbhai, Coureche Guillaume, Derangère, Valentin, Vincent, Julie, Chauffert, Bruno, Aubriot-Lorton, Marie Hélene, Farah, Wahlid, Mourier, Klaus Luc, Boidot, Romain, Ghiringhelli, Francois
• Format: Journal Article
• Language: English
• Published: United States Impact journals 25.10.2016; Impact Journals LLC
• Subjects: Age Factors; Angiogenesis Inhibitors - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab - therapeutic use; Biomarkers, Pharmacological - blood; Brain Neoplasms - blood; Brain Neoplasms - mortality; Brain Neoplasms - pathology; Brain Neoplasms - therapy; Cancer; Cellular Biology; Chemoradiotherapy; Clinical Research Paper; Disease-Free Survival; Female; Follow-Up Studies; Gene Expression Profiling; Glioblastoma - blood; Glioblastoma - mortality; Glioblastoma - pathology; Glioblastoma - therapy; Granulocyte Colony-Stimulating Factor - metabolism; Humans; Karnofsky Performance Status; Leukocyte Count; Life Sciences; Male; Middle Aged; Neoadjuvant Therapy - methods; Neoplasm Recurrence, Local - blood; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Neoplasm Recurrence, Local - therapy; Neovascularization, Pathologic - drug therapy; Neutrophils; Prognosis; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome; Vascular Endothelial Growth Factor A - antagonists & inhibitors; bevacizumab; glioblastoma; prognosistic factor; Phase-Ii Trial; Brain-Tumors; Single-Agent Bevacizumab; Colony-Stimulating Factor; Recurrent Glioblastoma; Malignant Glioma; Pretreatment Neutrophil; Newly-Diagnosed Glioblastoma; Endothelial Growth-Factor; To-Lymphocyte Ratio
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.10898

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.