PERAMPANEL-BTRE-META
(2026)Objective
To systematically evaluate the efficacy and safety of perampanel in patients with brain tumor-related epilepsy (BTRE), focusing on seizure control, oncologic outcomes, and tolerability.
Study Summary
• ≥50% seizure reduction in 46% (95% CI 31%–62%; I²=84.3%)
• Oncologic progression in 39% (95% CI 17%–65%; I²=0%) — no signal of perampanel effect on tumor behavior
• Adverse events in 26% (95% CI 17%–38%; I²=61.6%); most common: dizziness, somnolence, fatigue
Intervention
Perampanel (selective, noncompetitive AMPA glutamate-receptor antagonist), monotherapy or adjunctive, mean doses ~3.4–7.5 mg/day
Inclusion Criteria
Prospective or retrospective observational studies in adults with BTRE (primary or secondary brain tumor) evaluating perampanel with at least one efficacy or safety outcome
Study Design
Arms: Single-arm observational studies of perampanel (no control group)
Patients per Arm: 382 patients across 8 studies
Outcome
• ≥50% seizure reduction: 46% (95% CI 31–62%)
• Oncologic progression: 39% (95% CI 17–65%) with no evidence of perampanel effect on tumor behavior
• Adverse events: 26% (95% CI 17–38%), mostly mild-to-moderate; dizziness, somnolence, fatigue most common
Clinical Question
In adults with brain tumor-related epilepsy (BTRE), what is the pooled efficacy and safety of perampanel for seizure control and its effect on oncologic outcomes?
Bottom Line
Across 8 observational studies (n=382), perampanel achieved seizure freedom in 42% and ≥50% seizure reduction in 46% of BTRE patients, with adverse events in 26% (mostly mild-to-moderate) and no signal of an effect on tumor progression — supporting perampanel as a mechanistically targeted, non–enzyme-inducing option for BTRE.
Major Points
- Systematic review and meta-analysis of 8 observational studies (published 2017–2024) including 382 adults with brain tumor-related epilepsy treated with perampanel
- Pooled seizure freedom rate 42% (95% CI 27–59%; I²=65.7%, 7 studies); ≥50% seizure reduction 46% (95% CI 31–62%; I²=84.3%, 8 studies)
- Pooled oncologic progression 39% (95% CI 17–65%; I²=0%, 5 studies) — consistent with natural tumor history, no evidence of perampanel effect on tumor behavior
- Pooled adverse-event rate 26% (95% CI 17–38%; I²=61.6%, 8 studies); most frequent: dizziness, somnolence, fatigue
- Meta-regression: retrospective design associated with higher seizure-freedom rates (coef 1.03, p=0.035); AEs lower in retrospective cohorts (coef −1.03, p=0.040) and higher in IDH-mutant cases (coef −1.57, p=0.044); sample size and mean age were not associated with any outcome
- Mechanistic rationale: perampanel is a selective noncompetitive AMPA-receptor antagonist targeting glutamate-mediated peritumoral hyperexcitability that drives BTRE
- Non–enzyme-inducing profile makes perampanel attractive for co-administration with antineoplastic therapies (minimal drug–drug interactions)
- Limitations: all included studies were single-arm observational series, small samples, short/variable follow-up, English-only, and heterogeneous outcome definitions — precluding causal inference
Study Design
- Study Type
- Systematic Review and Meta-Analysis
- Randomization
- No
- Blinding
- Not applicable (meta-analysis of single-arm observational studies)
- Sample Size
- 382
- Follow-up
- Variable across included studies (not standardized)
- Centers
- 8
- Countries
- Italy, USA, Austria, Japan, France
Primary Outcome
Definition: Seizure freedom — proportion of patients seizure-free during follow-up (pooled random-effects meta-analysis; 7 studies)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| N/A (single-arm) | 42% pooled | - (27%–59%) | N/A |
Limitations & Criticisms
- All included studies were single-arm observational series — no control groups, precluding causal inference or estimation of relative treatment effects
- Small individual sample sizes (median cohort ~12; range 5–272) and relatively short follow-up periods
- Substantial statistical heterogeneity for seizure freedom (I²=65.7%) and ≥50% reduction (I²=84.3%)
- Heterogeneity in outcome definitions, follow-up duration, and adverse-event reporting across studies (measurement/reporting bias)
- Inconsistent reporting of perampanel dose, treatment duration, concomitant ASMs, and molecular tumor markers (IDH1, MGMT)
- Restriction to English-language publications introduced potential language bias
- Wide confidence intervals for some pooled estimates reflecting limited data
- Modest number of studies (k<10) limits reliability of publication-bias assessment (funnel plot, Egger test) and statistical power of meta-regression
- JBI critical appraisal flagged incomplete/non-consecutive inclusion of participants in several retrospective series (selection bias)
- One study (Nakai 2024) contributed the majority of patients (272/382, 71%) and dominated pooled AE and ≥50%-reduction estimates
Citation
Neurol Clin Pract 2026;16(4):e200636. DOI: 10.1212/CPJ.0000000000200636