Bevacizumab enhances overall survival in newly diagnosed glioblastoma patients with high COX-2 expression

Bevacizumab (BEV) is known to improve progression-free survival (PFS) but not overall survival (OS) for newly diagnosed glioblastoma (ndGBM). Here, we evaluated the survival outcomes between temozolomide (TMZ)-only and TMZ + BEV treatments stratified based on the cyclooxygenase-2 (COX-2) expression, a rate-limiting enzyme involved in the cancer development. Fifty IDH-wildtype ndGBM patients treated between 2012 and 2023 were enrolled in this study. Pretreatment levels of COX-2 protein and mRNA expression were quantified, and survival analyses were performed based on the immunoreactivity score (IRS). Patients with high COX-2 expression (IRS ≥ 3, determined by its median) also exhibited higher COX-2 mRNA levels (∆Ct 6.43 ± 1.64 vs. 7.67 ± 0.81; p = 0.020). In patients with high COX-2 expression, TMZ + BEV had significantly longer median PFS and OS than those receiving TMZ-only (PFS: 22 vs. 8 months, p < 0.001; OS: 25 vs. 18 months, p = 0.009). In contrast, these benefits were not found in patients with low COX-2 expression (PFS: 12 vs. 15 months, p = 0.875; OS: 24 vs. 26 months, p = 0.775). Altogether, this study suggests that patients with high, but not low, COX-2 expression demonstrate survival benefits from the addition of BEV in ndGBM.