Clinical safety and efficacy of bevacizumab in combination with mitogen-activated protein kinase kinase inhibitor therapy for glioma: a retrospective analysis

Abstract Background Mitogen-activated protein kinase kinase (MEK) and vascular endothelial growth factor (VEGF) inhibitors are both used to treat progressive, pediatric low-grade glioma (LGG), and VEGF inhibitors have been used to salvage vision in optic pathway glioma (OPG). The combination of these 2 drugs may be an effective bridge to salvage vision in progressive OPG; however, a paucity of data exists on synergistic toxicities. Methods We performed a retrospective multi-institutional cohort study to examine toxicity and visual acuity (VA) outcomes among patients treated with overlapping bevacizumab and MEK inhibitor therapy. Patients were included if they had a probable or biopsy-confirmed glioma of any location treated with overlapping treatment between 2010 and 2022. Toxicities potentially related to combination therapy were abstracted by chart review and graded by CTCAE, version 5. Results Seventeen patients received treatment with a combination of bevacizumab and MEK inhibitor for a median duration of 3.5 months (range 1-21). No unexpected toxicities were identified: 3 patients experienced a grade 3 toxicity (acneiform rash, proteinuria, and asymptomatic creatine kinase elevation); no grade 4 toxicities were identified. Of the 8 patients with OPG and evaluable VA, 3 (38%) either showed vision improvement or stabilization of a documented VA decline. No patients demonstrated worsened VA. Conclusions MEK inhibitor therapy with adjuvant bevacizumab appears to be safe in patients with progressive, treatment-refractory sporadic and NF1-associated glioma. A larger, prospective study would help establish the safety and efficacy of this combination as an alternate treatment approach to optimize visual outcomes for OPG.