Unmet Needs in PLGG: FGFR-Altered Tumors, Vision Preservation, and Long-Term Outcomes

In this closing segment, the panel identifies the most pressing unmet needs in pediatric low-grade glioma (PLGG) for the next 10 to 20 years.

FGFR-altered tumors emerge as the consensus next frontier. These tumors can present with catastrophic intratumoral hemorrhage and true malignant transformation, where an initially low-grade tumor becomes high-grade on repeat biopsy, suggesting they deserve "an asterisk" within the PLGG category. Some emerging data with mirdemetinib are noted, but effective targeted options remain limited. The unmet need extends to other uncommon molecular drivers, including MYB/MYBL1- and KRAS-mutated low-grade tumors, for which dedicated therapies are lacking.

Visual preservation in optic pathway tumors is identified as the greatest quality-of-life challenge. Current MEK inhibitors achieve a median time to response of approximately 5.3 months, which may be too slow to prevent irreversible vision loss. The panel calls for more effective agents with fewer side effects and faster responses, as well as better evidence on which therapies, and in what order, best protect vision.

Long-term outcome data represent a critical gap. Understanding when tumors become senescent, what morbidity trajectories look like across decades, and what second malignancy risks emerge would directly inform upfront treatment decisions. The PLGG/Pediatric Low-Grade Astrocytoma (PLGA) Coalition is actively gathering such data, and the panel finds the breadth of ongoing research across multiple aspects of low-grade gliomas encouraging.

Thank you for watching this OncLive Peer Exchange series on treatment decision-making in pediatric low-grade glioma. We hope you found it informative. Please subscribe to our newsletter for updates on upcoming episodes and new data.