LBA16 - Association of matrix metalloproteinase 2 (MMP2) plasma level with response and survival in patients treated with bevacizumab for recurrent high gra...

Date 01 October 2012
Event ESMO Congress 2012
Session CNS tumors
Presenter Emeline Tabouret
Authors E. Tabouret1, F. Boudouresque2, M. Barrié3, M. Matta3, C. Boucard3, A. Loundou4, M. Ouafik2, O. Chinot3
  • 1Neuro-oncology, AP-HM Timone, Marseille/FR
  • 2Umr 911, AMU, Marseille/FR
  • 3Neurooncology, AP-HM Timone, Marseille/FR
  • 4Santé Publique, AMU, Marseille/FR

Abstract

Background Predictive marker of bevacizumab activity is an unmet medical need, while activity of this anti-VEGF Mab is reported to be heterogeneous, particularly in glioblastoma. Objective To identify circulating biomarker that predicts response to bevacizumab and outcome in recurrent high grade glioma (HGG). Methods Eleven angiogenic makers were analyzed, using ELISA, at baseline and one month apart from bevacizumab initiation in a first cohort of 26 HGG patients of our institution (cohort 1); Plasma marker dosages were correlated to objective response (RANO criterias), Progression-free survival (PFS), and overall survival (OS). Correlations were validated in a separate cohort of 50 patients (Cohort 2). Markers analyses were performed in two other cohorts treated with cytotoxic agents up front (cohort 3 n=20) or concomitant to radiotherapy (cohort 4 n=24). Results In cohort 1, high MMP2 baseline level was associated to a probability of response of 83.3% versus 15.4% in case of low MMP2 level (p=0.001). By univariate analyses, confirmed by multivariate analysis, MMP2 correlated with PFS (p=0.007) and OS (p=0.001), as decrease of plasmatic VEGF level (p=0.038 for PFS and p=0.013 for OS) and MMP9 level (PFS p=0.016, OS p=0.025). These results were confirmed with a similar magnitude in cohort 2 for MMP2 only (p<0.0001 for response, p=0.009 for PFS and p=0.009 for OS). In cohort 3 and 4, no association was found between MMP2 and response, PFS, or OS. Conclusions Among patients with recurrent HGG treated with bevacizumab, but apparently not with cytotoxic agent, higher plasma MMP2 levels were associated with objective response, prolonged tumor control and survival. Further studies are needed to validate the predictive value of these/this biomarker(s) both with glioma and other cancers.