James T. Rutka Pediatric Brain Tumor Surgery Award: Cutaneous Toxicity Profiles of MEK Inhibitor Targeted Therapy for Pediatric Low Grade Gliomas

Introduction: Use of MEK inhibitors, including Trametinib and Selumetinib, have become increasingly common for treatment of pediatric low-grade gliomas (pLGGs). While their efficacies have been well validated, the variability of adverse event profiles and incidence remains unclear. Current published literature shows inconsistencies between the rates and severity of targeted therapy-induced toxicities, especially skin-related toxicities, and therapy discontinuance.

Methods: Pediatric patients with pLGGs treated at Connecticut Children’s between 2015 and 2022 were retrospectively reviewed. All patients treated with MEK inhibitors were included. Patients who experienced dermatologic toxicities were compared to the overall group of patients who received treatment. Grading of adverse events was determined by CTCAE version 5.0.

Results: Eighteen patients met the inclusion criteria for this study. Among these patients, 16 (88.9%) were treated with Trametinib only, 1 (5.6%) was treated with Trametinib and Dabrafenib and 1 (5.6%) was initially treated with Selumetinib; of those treated initially with Trametinib, 2 patients switched to Selumetinib due to cutaneous toxicity and 2 moved on to a combination treatment of Trametinib and Dabrafenib. All 4 patients with medication changes to Selumetinib or combination treatment showed decreased cutaneous toxicity. 13 (72.2%) patients experienced a skin toxicity, and 4 (22.2%) experienced a second type of cutaneous toxicity. 5 (27.8%) patients discontinued treatment due to their cutaneous toxicity, and 9 (50.0%) patients had their drug dosages limited or modified.

Conclusion : Our experience highlights the diversity in toxicity profiles of MEK inhibitors, as we report higher rates of cutaneous toxicity and toxicity-related discontinuation than those reported in previous literature. Outside of a clinical trial, and with other treatment options available, patients are more likely to discontinue or change therapy with cutaneous toxicity. This highlights the need for improved supportive care for cutaneous toxicity to allow our patients to benefit from the full panoply of modern treatment options for low grade glioma.