Management of adverse events in patients with pediatric low-grade glioma treated with MAPK-directed therapies: Delphi consensus recommendations and unmet needs

Background: Pediatric low-grade gliomas (pLGGs) are the most common childhood central nervous system (CNS) tumors. Targeted therapies are effective treatments in patients with pLGGs harboring mutations in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK) signaling pathway. Understanding the toxicity profile and tolerability of emerging MAPK inhibitors (MAPKi) and how adverse events (AEs) can be managed to avoid treatment discontinuation, interruption, or dose reduction is important for optimizing clinical benefit. Methods: A modified Delphi consensus initiative was conducted to provide recommendations on the monitoring and management of AEs that occur with MAPKi in patients with pLGG. A 9-member steering committee was convened to develop statements based on the findings of a comprehensive literature review of AEs reported with the use of MAPKi in pediatric cancers. Consensus on statements was determined via online surveys completed by a large, global panel of experts in pLGG. Results: Of the 129 statements drafted, consensus (≥75% agreement) among 82 global experts in pLGG was reached for 50 statements, mostly pertaining to the general management of AEs occurring with MAPKi and the management of cutaneous AEs. Consensus statements include guidance on skin care and specific cutaneous conditions. Many AEs were rare with limited evidence or experience to achieve consensus recommendations. Conclusions: The consensus statements developed provide guidance and recommendations for the management of common AEs in patients with pLGG treated with MAPKi. Sharing this knowledge may lead to patients with pLGG achieving optimal benefit from MAPKi while minimizing and effectively managing AEs.