Efficacy and safety of trametinib use in pediatric brain tumors in a low- to middle-income country.

PURPOSE: Trametinib, a mitogen-activated protein kinase (MEK) inhibitor, is a promising targeted therapy for children with progressive, unresectable low-grade gliomas (LGGs) who have failed standard chemotherapy regimens. There are limited data on the use of targeted therapy in Low-Middle-Income Countries (LMIC), and specifically, there are no published data from Lebanon on the use, efficacy, and safety of these agents. METHODS: A retrospective review of the medical records of pediatric patients with brain tumors who received trametinib at the LAU Medical Center Rizk Hospital was undertaken, along with a detailed data collection and a family interview to evaluate the quality of life of the patients while administering this agent. RESULTS: Four pediatric patients diagnosed with progressive LGGs, harboring distinct molecular drivers (KIAA1549-BRAF, NF1 Loss, and BRAF V600E), were identified. Age range at diagnosis was 11 months to 10 years. Trametinib was obtained on a compassionate basis through an international Managed Access Program. The median duration of trametinib use was 30.2 months (range 22 to 35.5 months). Clinical improvement was observed in all patients along with partial radiographic response in one patient. The most common side effects were skin reactions and gastrointestinal complaints, with few therapy interruptions required. Quality-of-life assessment using the Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales revealed significant heterogeneity, with physical and school function being the most affected. CONCLUSION: Despite few manageable side effects, the favorable outcomes on tumor response and quality of life of trametinib-based therapy in Lebanese pediatric LGG patients suggest that MEK inhibitors may be a feasible option in selected LMIC settings, when appropriate diagnostic and monitoring infrastructure is available.