Effects of Levetiracetam and Lacosamide on survival and seizure control in IDH-wild type glioblastoma during temozolomide plus radiation adjuvant therapy

Introduction: There are no clear indications for the best choice of anti-seizure medications to control brain tumor related epilepsy. In vitro studies have shown an antitumoral effect of Levetiracetam and Lacosamide on glioblastoma IDH-wild type. Research question: This study investigates whether the use of levetiracetam and/or lacosamide impacts survival rates. The secondary aim was to evaluate the efficacy of both ASMs in controlling seizures. Materials and methods: In this observational retrospective single-cohort study, patients underwent chemoradiation protocol after GBM surgery. They were grouped as follows: (1) use of levetiracetam, (2) use of lacosamide, (3) simultaneous use of levetiracetam and lacosamide, (4) no ASM usage. Survival curves were plotted using the Kaplan-Meier method coupled with a log-rank test for difference assesments. To evaluate the pharmacological efficacy of post-operative seizure control, a negative binomial regression was conducted. Results: The study included 272 patients, 174 of which underwent adjuvant chemoradiation treatment. Patients without ASM therapy had a non-significant longer median OS (compared to the other groups (log-rank = 0.37). The IRR of seizure relapse was 2.57 (p = 0.007) times higher in lacosamide users, and MGMT promoter methylation demonstrated a protective effect against postoperative seizure onset (p = 0.05), regardless of the aforementioned confounding factors. Discussion and conclusions: In patients diagnosed with GBM IDH-WT undergoing chemoradiation therapy, the use of levetiracetam or lacosamide for controlling BTRE does not seem to modify survival. Lacosamide users exhibited a higher IRR of postoperative seizures compared to levetiracetam users, and MGMT promoter methylation appears to be a protective factor.