Lacosamide in monotherapy in patientswith BTRE: a multicentric retrospective

studyFrancesca Mo

U.O Neuro-Oncologia, Dipartimento di NeuroscienzeCittà della Salute e della Scienza e Università di Torino

Spring Meeting, Roma 25 Maggio 2019

Introduction

• Lacosamide in an antiepileptic drug indicated in partial onset epilepsy(with or without secondary generalization) of adults and adolescentsaged >= 16 years old.• Approved from 2008 in add-on therapy, from 2014 in monotherapy in

US and from 2017 in Europe• LCM modulates voltage-gated sodium channels by enhancing their

slow inactivation• In addition, LCM seems to interact with collapsine-response mediator

protein 2 and thus may mediate neuronal plasticity

Chistoph Kellinghaus, Ther Clin Risk Manag. 2009

Pharmacokinetics• Half-life of 13 hours• No relevant protein binding (< 15%)• No induction or inhibition of cytochrome P450 system• No clinically significant drug-drug interactions• Starting dose 50 mg twice a day, with titration up to a maximum of

400 mg per day in add-on therapy and up to a maximum of 600 mg per day in monotherapy. • LCM and its metabolites are eliminated primarily by kidney• In patients with eGFR < 30 ml/min (IRC stadium IV-V), maximum

dosage admitted 250 mg per day

Chistoph Kellinghaus, Ther Clin Risk Manag. 2009

Trials of lacosamide in add-on therapy in non BTRE

Sebastian Bauer et al, November 9, 2016

Adverse events

Sebastian Bauer et al, November 9, 2016

Add-on Lacosamide in BTREAuthor Type of Study No. Histology ↓ > 50% Seizure

freeSide effects Follow-up

(median)

Maschio et al, Epilepsy and Behavior, 2017 Prospective 25 Gliomas (gr II, III, IV) 86,4 % 32% DizzinessBlurred vision

6

Saria et al, J of Neurosurg, 2013 Retrospective 70 Gliomas (gr II, III, IV)Meningiomas

Ependymomas

66%(any reduction)

Fatigue 6

Villanueva et al, Epilepsy & Behavior, 2016 RetrospectiveMulticentric,

Real-life study (14 Centers)

106 Gliomas (gr II, III, IV)Meningiomas

EpendymomasGlioneuronal tumours

Brain metastases

66% 31% SomnolenceDizzinessFatigue

6

Rudà et al, J of Neurooncol, 2017 Prospective 71 Gliomas (gr II, III, IV) 76% 43% Dizziness 9

• 71 pazients enrolled in the study

• Seizure reduction >=50% at 3-6-9 months in 74,6%, 76% and 86,2% of patientsrespectevely

• Seizure freedom at 3-6-9 months in 42,2%, 43% and 50% of patients respectevely

• Maximum seizure control with doses of 250 mg/die of LCM (60% of patients)

• Better seizure control in patients with first add-on therapy rather than later add-on therapy

• In some patients, seizure reduction despite of tumor progression at MRI

PROPOSAL

A multicentric retrospective study for LCM in monotherapyin patients with BTRE

• Aim of the study: to assess the efficacy and tolerability of LCM

• Inclusion criteria:

Ø Age ≥ 16 year-old

Ø Any brain tumor type (primary or secondary)

Ø At least two partial onset seizures (with or withouth secondary generalization)

Ø Lacosamide used in monotherapy ab initio or secondary conversion to monotherapy (after

withdrawal of other AEDs)

Come parteciparel I Centri interessati a partecipare allo studio possono contattarci ai seguenti recapiti mail:

q francesca.mo374@edu.unito.itq rudarob@hotmail.com

l Verrà inviato il Database da compilare e da reinviare agli indirizzi mail sopra riportati entro il 30 Settembre 2019 (data prevista per la chiusura dello studio)

l Seguirà l’analisi definitiva dei dati

Grazie per l’attenzione