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

Abstract

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.

Keywords: Anti-Seizure medication; Brain tumor related epilepsy; Epilepsy; Glioblastoma; Lacosamide; Levetiracetam.

Fig. 1

Descriptive diagram of inclusion criteria and patient selection.

Fig. 2

Kaplan-Meier survival curves for patients who took only levetiracetam (blue line), only lacosamide (red line), both levetiracetam and lacosamide (green line), and neither of the two drugs (orange line). For comparison between the curves, log-rank test's p-value is reported. Lev = levetiracetam, Lac = lacosamide.

Fig. 3

Kaplan-Meier survival curves for patients who took only levetiracetam full-time (blue line) or part-time/never (red line). For comparison between the two curves, log-rank test's p-value is reported. Lev = levetiracetam.