Associations of anticoagulant use with outcome in newly diagnosed glioblastoma

Emilie Le Rhun, Els Genbrugge, Roger Stupp, Olivier L Chinot, L Burt Nabors, Timothy Cloughesy, David A Reardon, Wolfgang Wick, Thierry Gorlia, Michael Weller,

Eur J Cancer

https://doi.org/10.1016/j.ejca.2018.06.029

Abstract

Background: To test the hypothesis that despite bleeding risk, anticoagulants improve the outcome in glioblastoma because of reduced incidence of venous thromboembolic events and modulation of angiogenesis, infiltration and invasion. Methods: We assessed survival associations of anticoagulant use from baseline up to the start of temozolomide chemoradiotherapy (TMZ/RT) (period I) and from there to the start of maintenance TMZ chemotherapy (period II) by pooling data of three randomised clinical trials in newly diagnosed glioblastoma including 1273 patients. Progression-free survival (PFS) and overall survival (OS) were compared between patients with anticoagulant use versus no use; therapeutic versus prophylactic versus no use; different durations of anticoagulant use versus no use; anticoagulant use versus use of anti-platelet agents versus neither anticoagulant nor anti-platelet agent use. Cox regression models were stratified by trial and adjusted for baseline prognostic factors. Results: Anticoagulant use was documented in 75 patients (5.9%) in period I and in 104 patients (10.2%) in period II. Anticoagulant use during period II, but not period I, was associated with inferior OS than no use on multivariate analysis (p = 0.001, hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.18-1.95). No decrease in OS became apparent when only patients with prophylactic anticoagulant use were considered. No survival association was established for anti-platelet agent use. Conclusions: Anticoagulant use was not associated with improved OS. Anticoagulants may not exert relevant anti-tumour properties in glioblastoma.