Abstract The clinical trial landscape of molecularly targeted treatments for pediatric low-grade glioma (pLGG) has created an exciting and hopeful era for both patients and clinicians alike. Despite numerous clinical trials investigating the use of targeted agents for pLGG, only two oral precision-based regimens for pLGG have received federal agency approval. However, enthusiasm surrounding recently completed early phase clinical trials has resulted in increased off-label prescribing practices beyond the federally-approved indications, despite a lack of phase 3 clinical trial data and an incomplete understanding of the long-term radiographic, functional outcomes, and toxicity for both approved and experimental therapies. These gaps in knowledge are critically important to consider when selecting therapies for patients with pLGG, as the prevention and reduction of late effects in pLGG survivors is crucial to prevent long-term morbidity. In this editorial by the clinical working group of the International pLGG Coalition, we discuss the landscape of molecularly targeted therapies for pLGG, outline the unanswered questions for the use of novel therapies in the management of pLGG, review the risks and benefits of early off-label use of targeted agents, and discuss the importance of patience and evidence-based clinical practice in the rapidly evolving era of precision medicine.
Kotch et al. (Sat,) studied this question.