Effectiveness and tolerability of lacosamide as add‐on therapy in patients with brain tumor–related epilepsy: Results from a prospective, noninterventional study in European clinical practice (VIBES)

Abstract

Objective: To evaluate the effectiveness and tolerability of lacosamide added to one or two antiepileptic drugs (AEDs) in the treatment of patients with brain tumor-related epilepsy (BTRE), and to evaluate patients' global impression of change and quality of life (QoL). Methods: This was a prospective, multicenter, single-arm, noninterventional study with a 6-month observation period (EP0045; NCT02276053). Eligible patients (≥16 years old) had active BTRE secondary to low-grade glioma (World Health Organization grade 1 and 2) and were receiving treatment with one or two AEDs at baseline. Lacosamide was initiated by the treating physician in the course of routine clinical practice. Primary outcomes were 50% responders (≥50% reduction in focal seizure frequency from baseline) and Patient's Global Impression of Change (PGIC) at month 6. Secondary outcomes included seizure-free status and Clinical Global Impression of Change (CGIC) at month 6, change in QoL (5-Level EuroQol-5 Dimension Quality of Life Assessment) and symptom outcomes (MD Anderson Symptom Inventory-Brain Tumor) from baseline to month 6, and Kaplan-Meier estimated 6-month retention on lacosamide. Safety variables included adverse drug reactions (ADRs). Results: Patients were recruited from 24 sites in Europe. Ninety-three patients received lacosamide (mean [standard deviation] age = 44.5 [14.7] years; 50 [53.8%] male; median baseline focal seizure frequency = five seizures/28 days [range = 1-280]), of whom 79 (84.9%) completed the study. At 6 months, 66 of 86 (76.7%) patients were 50% responders and 30 of 86 (34.9%) were seizure-free. Improvements on PGIC were reported by 49 of 76 (64.5%) patients. Based on CGIC, 52 of 81 (64.2%) patients improved. QoL and symptoms outcome measures remained stable. 648 | RUDÀ et al.

Clinical Management of Diffuse Low-Grade Gliomas

“…When an add-on therapy is required, the combination of levetiracetam and valproic acid proved to be the most effective [ 144 ]. Favorable effects in add-on therapy were demonstrated, or emerged from preliminary data, also for the most recently marketed AEDs, such as lacosamide, lamotrigine, zonisamide, perampanel, and eslicarbazepine [ 146 , 149 , 150 , 151 , 152 ]. Lacosamide emerged as a valid alternative in focal seizures also in monotherapy [ 153 , 154 ], but solid evidence on large LGG population is still expected.…”

The effectiveness of antiepileptic drug treatment in glioma patients: lamotrigine versus lacosamide

“…Lamotrigine had improved efficacy over frequently used second-line AEDs like carbamazepine for time to treatment failure for any reason [ 15 , 16 , 28 , 29 ]. Lacosamide demonstrated relatively high effectiveness as add-on therapy in BTRE, with 6-month retention rates up to 86% [ 19 – 21 , 30 , 31 ]. The anticonvulsive action mechanism of lamotrigine, a voltage-gated sodium channel blocker, is due to the inhibition of glutamate excitotoxicity [ 32 ].…”

“…Lamotrigine has proven to be effective in non-BTRE, both as monotherapy and as addon therapy [14][15][16][17][18]. Lacosamide can significantly improve seizure control and is well tolerated as add-on therapy in the non-BTRE population too, therefore being frequently prescribed to patients with glioma [19][20][21]. Currently, there are no studies that have compared the effectiveness of lamotrigine versus lacosamide in glioma patients with epilepsy.…”

Seizures, Edema, Thrombosis, and Hemorrhages: An Update Review on the Medical Management of Gliomas

“…Neuropsychiatric effects, like anxiety, irritability or psychosis, are not uncommon, especially in frontal lobe tumors ( 58 , 59 ). Recently lacosamide, a sodium channel blocker, has been increasingly reported as an add-on drug in BTRE with good efficacy and tolerability ( 60 , 61 ). Other drugs approved for focal epilepsy have been tested in BTRE and can be an option especially for add-on therapy, like topiramate ( 62 ), pregabalin ( 63 ), and oxcarbazepine ( 64 ).…”