10080- COT-9 HIGH EXPRESSION OF COX-2 PREDICTS IMPROVED OVERALL SURVIVAL OUTCOME IN BEVACIZUMAB-TREATED HIGH-GRADE GLIOMA PATIENTS

Abstract INTRODUCTION Studies have shown that bevacizumab (BEV) improves progression-free survival (PFS) but not overall survival (OS) in high-grade glioma (HGG) patients. Here we evaluate the potential of cyclooxygenase-2 (COX-2), a rate-limiting enzyme involved in inflammation and tumor progression by producing prostaglandin E2, as a differentiating factor for the subset of participants who benefit from BEV treatment. METHODS We performed a retrospective study on newly diagnosed HGG patients who received Temozolomide (TMZ) alone or TMZ+BEV chemotherapy. We assessed the expression of COX-2 using immunohistochemistry staining prior to receiving chemotherapy. An immunoreactivity score > 3 is considered high. We performed survival analysis on PFS and OS among patients with high vs. low expression. RESULTS A total of 60 patients were enrolled in our study, with 28 treated with TMZ only and 32 treated with TMZ+BEV. We found 36 patients with low expression and 24 patients with high expression. High expression of COX-2 is known to be associated with poor prognosis for HGG patients. Here we found no significant differences in median PFS and OS between low and high expression of COX-2 among those receiving TMZ+BEV (PFS: 22 vs. 18 months, p=0.95; OS: 25 vs. 25 months, p=0.53). Interestingly, among patients with high expression of COX-2, those receiving TMZ+BEV showed significantly higher median PFS and OS than the TMZ only group (PFS: 18 vs. 8 months, p=0.001; OS: 25 vs. 14 months, p=0.022). This difference was not identified in patients with low expression of COX-2 between the TMZ+BEV vs. TMZ only groups (PFS: 22 vs. 10 months, p=0.16; OS: 25 vs. 20 months, p=0.09). CONCLUSION Our data demonstrate the benefit of BEV chemotherapy for HGG patients with high expression of COX-2, thus supporting the use of COX-2 as a predictive biomarker for determining which HGG patients are likely to benefit from BEV chemotherapy.