Ctni-26. efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial

Abstract Glioblastoma(GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of meformin in patients with recurrent or refractory GBM treated with low-dose temozolomide (TMZ). Included patients were randomly assigned to a control group [placebo plus low-dose TMZ (50mg/m2, daily) or and experimental group [metformin (1,000mg, 1,500mg, and 2,000mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose TMZ]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety. Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI:12.19-21.68 months) in the experimental group and 7.69 months (95% CI: 5.16-22.67 months) in the control group, showing no significant difference by the log-rank test (HR:0.78; 95% CI:0.39-1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.3% in the experimental group, respectively. Although the metformin plus TMZ regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM.