NCOG-38. LAMOTRIGINE MONOTHERAPY ASSOCIATES WITH IMPROVED PROGRESSION-FREE AND OVERALL SURVIVAL IN HIGH-GRADE GLIOMA

Abstract BACKGROUND High-grade gliomas (HGG) are aggressive brain tumors with notoriously poor prognoses and high symptomatic burden, including seizures in 30-60% of HGG cases. Despite negative impacts to quality of life, positive seizure history at presentation and during the disease course has been shown to associate with improved overall survival. Further, recent preclinical studies have suggested a link between neuronal hyperexcitation and more rapid glioma progression. We hypothesized anti-seizure medication (ASM) therapy may suppress neuronal excitation and therefore help prolong survival. To this aim, we characterized the association of various ASM therapies with survival and seizure control. METHODS Retrospective review of 413 patients with co-occurring HGG and clinically diagnosed epileptic activity. Multivariable linear regression was used to assess the impact of ASM quantity (monotherapy versus polytherapy) and type (specific ASMs as well as ASM class) on progression-free survival (PFS) and overall survival (OS). Logistic regression was used to assess the impact of ASM quantity and type on likelihood of achieving seizure remission. Additional variables in the regressions included age, treatment exposure (radiation therapy, cytotoxic chemotherapy, or targeted chemotherapy), and extent of surgical resection (gross total resection versus all other surgeries). Kruskal-Wallis tests were used to compare median survival between multiple groups. RESULTS ASM monotherapy and polytherapy demonstrated comparable survival outcomes. Among patients who received ASM monotherapy, only lamotrigine demonstrated a significant association with improved survival with PFS and OS (P = <0.001 for both). No specific drug or drug class demonstrated greater likelihood of achieving seizure remission. CONCLUSION Lamotrigine demonstrates a unique association with improved outcomes that is neither shared by other ASMs nor explained by ASM drug class, without any decline in likelihood of achieving seizure remission. Optimization of ASM therapy may enhance survival outcomes without compromising seizure control.