EP10.01 CLINICAL EFFICACY/EFFECTIVENESS, SAFETY AND HEALTH-RELATED QUALITY OF LIFE ASSOCIATED WITH TREATMENTS FOR RELAPSED/REFRACTORY PAEDIATRIC LOW-GRADE GLIOMA: A SYSTEMATIC LITERATURE REVIEW

Abstract BACKGROUND Patients with relapsed/refractory paediatric low-grade glioma (R/R pLGG) face considerable long-term morbidity. Most cases are driven by single-gene alterations in the mitogen-activated protein kinase (MAPK) pathway for which several targeted agents are being evaluated. Systematic literature reviews (SLRs) were performed to deepen understanding of the efficacy/effectiveness, safety and health-related quality of life (HRQoL) evidence for therapies in R/R pLGG, and to inform Health Technology Assessment (HTA) submissions for tovorafenib, a type II pan-RAF inhibitor. METHODS MEDLINE, Embase, CENTRAL, CDSR and DARE databases were searched up to 25 November 2024 with additional manual searches of key conferences, HTA reports, trial registries and regulatory documents in January 2025. Clinical trials and real-world (RW) studies of patients with R/R pLGG meeting predefined criteria were eligible (PROSPERO registration, CRD420250648339). Risk of bias was assessed. Findings were summarized narratively. RESULTS In total, 30 clinical trials (20 single-arm, 7 non-randomized, 3 randomized) and 14 RW studies (13 retrospective, 1 prospective) were included. Most clinical trials evaluated MAPK inhibitors (n = 15, including pan-RAF inhibitor tovorafenib [n = 2] and V-Raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor dabrafenib [n = 2]) or chemotherapy-based regimens (n = 13; 12 regimens). Most RW studies evaluated chemotherapy-based regimens (n = 10; 18 regimens), one evaluated RAF/BRAF inhibitors. The majority of MAPK inhibitor studies reported the distribution of patients with BRAF alterations and often reported stratified outcomes. In contrast, only one clinical trial of a chemotherapy-based regimen reported BRAF alteration status; stratified outcomes were not reported. Between-study comparisons were complicated by limited patient characteristics and/or subgroup reporting, and where reported, by heterogeneity in populations and methodologies used for assessing outcomes. Specifically, in clinical trial BRAF-altered populations, overall response rates ranged from 15-69% and median progression-free survival from 14-37 months. Across drug classes, fatigue was a frequently reported adverse event of special interest. No HRQoL data were found. Functional outcomes of increasing clinical interest were out of scope of the SLRs. CONCLUSION The variety of therapies identified highlights a lack of standard of care for R/R pLGG and a need for specific, well-tolerated treatment options with proven efficacy/effectiveness that improve HRQoL/functional outcomes. Future studies that report molecular prognostic factors (e.g. BRAF alterations), employ consistent efficacy/effectiveness and safety assessments, and evaluate long-term treatment impact on HRQoL/functional outcomes are needed to guide treatment selection.