Levetiracetam associated with longer OS in IDH wild-type glioblastoma

An observational single-institution cohort study provides evidence that levetiracetam use throughout the duration of standard chemotherapy is associated with longer median overall survival (OS) in patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma.

“Epileptic seizures occur in 30–60 percent of patients with IDH wild-type glioblastoma, necessitating long-term use of antiepileptic drugs,” wrote the investigators. [Neurology 2017;88:1805-1813; Epilepsia 2013;54:12-17] “Therefore, antiepileptic drugs are often combined with temozolomide during the standard combined chemoradiation protocol.”

Of the 460 patients with newly diagnosed IDH wild-type glioblastoma included in the study, 162 patients (35.2 percent) had epileptic seizures and 171 patients (37.2 percent) were taking at least one antiepileptic medication. In the cohort, 116 patients took levetiracetam for the duration of chemoradiation, 126 took it part of the time and 218 never took it. Patients who used levetiracetam for the duration of standard chemoradiation were case-matched 1:1 to those who used it part or none of the time, while on chemoradiation. [Neurology 2021;doi:10.1212/WNL.0000000000013005]

“Median OS was longer in patients who used levetiracetam throughout the whole duration of the standard chemoradiation protocol [21.0 months] than in patients with part-time levetiracetam use [16.8 months], and in patients who never received levetiracetam [16.0 months] [p=0.027]. After case-matching [n=54 per group], a longer OS was found for levetiracetam use during the whole duration of the standard chemoradiation protocol [hazard ratio (HR), 0.63; 95 percent confidence interval (CI), 0.42 to 0.94; p=0.023],” reported the researchers.

Levetiracetam use during the whole duration of the standard chemoradiation protocol (adjusted HR, 0.69; 95 percent CI, 0.52 to 0.93; p=0.014), O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation (adjusted HR 0.53; 95 percent CI, 0.39 to 0.71; p<0.001), and gross total tumour resection (adjusted HR, 0.57; 95 percent CI, 0.44 to 0.74; p<0.001) were all independent predictors of a longer OS.

“Since epileptogenic and oncogenic processes are intermixed in cerebral diffuse gliomas, an antiepileptic drug can have antitumour effects in addition to its effectiveness against epileptic seizures,” explained the researchers. “This has practical implications, as an antiepileptic drug, such as levetiracetam, can be introduced to the treatment regimen as an antitumor adjunct in combination with temozolomide during the standard chemoradiation protocol of IDH wild-type glioblastoma patients.”

“This study provides Class III evidence that in individuals with IDH wild-type glioblastoma, levetiracetam use throughout the duration of standard chemotherapy is associated with longer median OS. At a time when several antiepileptic drugs, such as sodium valproate, perampanel and levetiracetam, have been suggested to affect IDH wild-type glioblastoma prognosis, further prospective multicentre controlled trials aiming at investigating the survival benefit of each of these drugs should be considered,” they concluded. [Clin Neurol Neurosurg 2018;174:149-155; J Pers Med 2021;11:390; Sci Rep 2020;10:10783]