EPID-28PROGNOSTIC AND PREDICTIVE BIOMARKERS IN RECURRENT WHO GRADE 3 GLIOMA PATIENTS TREATED WITH BEVACIZUMAB AND IRINOTECAN

Abstract

BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients. The primary endpoint of this study was to identify predictive biomarkers associated with response to bevacizumab therapy. The secondary endpoint was to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS). METHODS: A total of 62 consecutive, recurrent grade 3 glioma patients were administered bevacizumab and irinotecan between December 2005 and November 2014 according to a previously published clinical protocol. A wide range of clinical, histopathological and molecular factors were screened for significant correlation (p < 0.05) with response and survival endpoints using logistic and Cox regression, respectively. Potentially predictive biomarkers were subjected to multivariate analysis. The landmark method was employed for analysis of survival by response. RESULTS: Twenty-two of 57 evaluable patients (38.6 %) demonstrated a response at the time of their best response MRI (RANO criteria). Responders had significantly prolonged OS (p = 0.007) and trended toward longer PFS (p = 0.067) as compared to non-responders (OS: 12.4 vs 4.3 months, PFS: 5.6 vs 3.2 months). A favorable WHO performance status (PS) and absence of necrosis were significantly more common in responders than non-responders. Multivariate analysis also identified a poor PS as the only prognostic factor for PFS, while an unfavorable PS and immunohistochemical p53 accumulation were prognostic of reduced OS. CONCLUSIONS: A poor baseline PS and the presence of necrosis were negatively associated with response to bevacizumab. An unfavorable PS and p53 positivity are prognostic of worse outcome in this patient population.