Gabapentin repurposing for glioblastoma therapy: Real-world data analyses augmented by use of active comparators

Glioblastoma hijacks neuronal pathways to drive tumor growth, and drugs affecting the function of these pathways may potentiate survival gains. Recent studies have suggested clinical benefits with post-diagnostic use of gabapentin. We assessed the impact of taking gabapentin after glioblastoma diagnosis utilizing an active comparator model in a population-based dataset of older adults in the United States. We leveraged a cohort of glioblastoma patients >65 years old who received resection, radiation, and temozolomide from the Surveillance, Epidemiology and End Results data paired with Medicare claims. Those receiving post-diagnostic gabapentin (TMZ+G) were compared to those receiving standard of care treatment only (TMZ), and two active comparators (duloxetine [TMZ+D], and levetiracetam [TMZ+L]). Association between medication use and overall survival was assessed using cox proportional hazards models adjusted for known prognostic factors. Out of 2,494 individuals, 797 (32%) received TMZ, 146 (5.9%) received TMZ+G, 38 (1.5%) received TMZ+D, and 1,513 (60.7%) received TMZ+L. Median survival among those receiving TMZ (10 months) as compared to all other groups (TMZ+G=16.3 months, TMZ+D=16 months; TMZ+L=13.0 months). TMZ+G was associated with 47% decrease in hazard of death (p<0.001) compared to TMZ, and a 32% decrease (p<0.001) compared to TMZ+L. Women had a 43% decrease in hazard of death (p<0.001) in TMZ+G as compared to TMZ+L, while this difference was non-significant in men (p=0.204). These results show survival benefit associated with gabapentin and supports ongoing work therapeutically targeting neuron-glioma interactions.