867 Postoperative Metformin is Associated With Improved Survival of Glioblastoma Patients

INTRODUCTION: Metformin may improve clinical outcomes for glioblastoma (GBM) patients as metformin showed in vitro tumor suppressor functions, such as reducing the proliferation of GBM tumor-initiating cells by reversing Akt kinase activation. METHODS: A single-centre retrospective study of 288 patients who underwent biopsy or surgery for GBM between 2014-2018 was conducted. Postoperative metformin treatment includes patients who received metformin as part of an adjuvant therapy with temozolomide and/or hyper-fractionated radiotherapy. Kaplan-Meier curves and log-rank p test were used for univariate analysis. Cox-proportional hazards model was used to generate adjusted hazard ratios with 95% CI for multivariate analysis. RESULTS: Metformin use impacted OS of patients with MGMT-methylated (MGMTm+) tumors (n = 71 no metformin (Met-), n = 35 metformin use (Met +); median OS = 442 vs. 662 days; p = 0.13) but not in patients with unmethylated MGMT tumors (n = 104 Met-, n = 44 Met+; median OS = 279 vs 295 days; p = 0.674). Postoperative metformin treatment of MGMTm+ tumor patients improved OS when compared to no or only preoperative metformin treatment (n = 66 no or preoperative metformin use, n = 40 postoperative metformin use; median OS = 443 vs 595; p = 0.012). Further, postoperative metformin treatment of nondiabetic patients with MGMTm+ tumors improved OS (n = 70 Met-, n = 18 postoperative Met+; median OS = 422 vs 582; p = 0.017). A multivariable model considering age, Karnofsky Performance Status (KPS), and extent of resection (EOR), demonstrated that postoperative metformin improves OS of MGMTm+ patients (aHR 0.500, 0.287-0.872, p = 0.015). Comparing postoperative with no or preoperative use of metformin produced a similar effect on OS (aHR 0.411, 0.177-0.954, p = 0.038). Postoperative treatment of nondiabetic patients with MGMTm+ tumors demonstrated improved OS (aHR 0.367, 0.156-0.864, p = 0.022). CONCLUSIONS: Postoperative metformin treatment of patients with MGMTm+ tumors is associated with improved OS, irrespective of age, diabetic status, KPS, or EOR.