Real-world comparative outcomes of including levetiracetam with standard treatment in glioblastoma multiforme: A multi-center retrospective cohort study.

e14055 Background: Despite standard therapy temozolamide (TMZ), overall survival in Glioblastoma multiforme (GBM) remains poor. Several studies have suggested levetiracetam (LEV) may enhance survival and outcomes, but its use remains controversial due to conflicting studies. This is a real world study using the TriNetX database to evaluate whether adding LEV to TMZ improves survival. Methods: This retrospective study used the TriNetX database (January 2005 to December 2024) to evaluate adult patients with GBM. Outcomes were compared between patients receiving TMZ only vs TMZ and LEV. Patients underwent 1:1 propensity matching on age at index, race, comorbidities, and treatment history. Overall survival (OS) was compared using a Kaplan-Meier survival analysis while risk differences and z-tests were used to compare cytopenia and rehospitalization outcomes. Results: After matching, each cohort was reduced to 401 patients, achieving demographic balance as follows: age (mean 60.5 ± 12.5 vs 60.8 ± 13.8), sex (56.9% male vs 57.4% male), and white race (83.0% vs 84.3%). Median OS was comparable in TMZ + LEV vs TMZ only groups (539 days vs 508 days, HR = 1.02, 95% CI: 0.84 - 1.23, p = 0.28), with survival probabilities of 15.4% and 16.9%, respectively, at the end of the time window. Severe cytopenia was significantly more common in the TMZ + LEV group (9% vs 4%, p = 0.004). Rehospitalization was more common in the TMZ + LEV group but did not reach statistical significance (13.22% vs 9.48%, Risk Difference 3.74% with 95% CI: 0.64 - 8.12, p = 0.095). Conclusions: In a propensity-matched real world cohort, levetiracetam use in combination with temozolamide was not associated with improved overall survival and was linked to a higher rate of severe cytopenia compared to temozolamide alone. These findings add real-world evidence to the existing literature, though limitations exist with retrospective studies thus supporting the need for additional prospective studies to clarify the impact of LEV on GBM outcomes.