Impact of levetiracetam use in glioblastoma: an individual patient-level meta-analysis assessing overall survival – PubMed Black Hawk Supplements

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CONCLUSIONS: This meta-analysis highlights that Lev use may prolong survival in IDH wild-type GB patients. Further randomized trials are needed to confirm these findings and identify subgroups benefiting most from Lev treatment.
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Impact of levetiracetam use in glioblastoma: an individual patient-level meta-analysis assessing overall survival - PubMed

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Impact of levetiracetam use in glioblastoma: an individual patient-level meta-analysis assessing overall survival

Martin Vychopen et al. Neurosurg Rev. .

Abstract

Background: Levetiracetam (Lev), an antiepileptic drug (AED), enhances alkylating chemotherapy sensitivity in glioblastoma (GB) by inhibiting MGMT expression. This meta-analysis evaluates Lev’s impact on GB treatment by analyzing overall survival of individual patient data (IPD) from published studies.

Methods: IPD was reconstructed using the R package IPDfromKM. Pooled IPD Kaplan-Meier charts of survival stratified by Lev therapy were created using the R package Survminer. One- and two-stage meta-analyses of Lev treatment regarding survival was performed.

Results: Three articles covering 825 patients were included out of 3567 screened records. Lev usage prevalence was 0.36. IPD from 590 IDH wild-type glioblastomas, with a median follow-up of 16.1 months, were utilized. Pooled data revealed median survival times of 19.2 months (95%CI: 16.4-22.0) for Lev users versus 16.5 months (95%CI: 15.2-17.8) for partial/no use (p = 0.006). One-stage meta-analysis indicated a significant association between Lev use and survival in IDH wild-type GB (HR: 1.33, 95%CI: 1.08-1.64, p = 0.007). Two-stage meta-analysis confirmed these results.

Conclusions: This meta-analysis highlights that Lev use may prolong survival in IDH wild-type GB patients. Further randomized trials are needed to confirm these findings and identify subgroups benefiting most from Lev treatment.

Keywords: Anti-epileptic drug; Glioblastoma; Individual Patient Data; Levetiracetam; Overall survival.

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Conflict of interest statement

Declarations. Ethics approval/study registration: This study is a meta-analysis and ethical approval was waived due to secondary data analysis. The study protocol was prospectively registered in the ‘International Prospective Register of Systematic Reviews’ (PROSPERO, Registration ID: CRD42024507697). Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1

Prisma flow diagram illustrating the study selection process

Fig. 2
Fig. 2

Kaplan–Meier chart displaying survival probability stratified by continuous levetiracetam use (turquoise) and no/partial levetiracetam use (red) in high-grade gliomas. The log-rank test (p = 0.03) showed a significantly enhanced survival time in those patients with continuous levetiracetam use. The shadowed areas surrounding the plots display the confidence intervals

Fig. 3
Fig. 3

Kaplan–Meier chart sowing survival probability stratified by continuous levetiracetam use (turquoise) and no/partial levetiracetam use (red) in IDH wild-type WHO grade 4 glioblastomas. The log-rank test (p = 0.0061) showed a significantly enhanced survival time in those patients with continuous levetiracetam use. The shadowed areas surrounding the plots display the confidence intervals.greater the weight of the study. The diamond corresponds to the logHR of the pooled data

Fig. 4
Fig. 4

Forest plot displaying log (Hazard ratio), log (Standard error), HR, and 95% CI estimates for OS in a fixed effect with the inverse variance method of the included studies for analysis of IDH wild-type WHO grade 4 glioblastoma. X-axis locations of squares label the hazard ratio. The weight of the included investigations is also reported. The diamonds constitute the hazard ratios of the pooled cohort in each model

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Impact of levetiracetam use in glioblastoma: an individual patient-level meta-analysis assessing overall survival – PubMed