LGG-20. SELUMETINIB IN PEDIATRIC PATIENTS WITH RELAPSED/REFRACTORY OPTIC PATHWAY/HYPOTALAMIC LOW GRADE GLIOMA: A MONOINSTITUTIONAL EXPERIENCE

Abstract

Abstract BACKGROUND Pediatric low-grade gliomas (pLGG) are the most common central nervous system tumors in children. The optic pathway and hypothalamic (OPH) frequent localizations are correlated with multiply relapses due to inoperability, thus emphasizing the need for alternative treatments. The results of activation of the BRAF oncogene through a tandem duplication resulting in a KIAA1549–BRAF fusion is the most common genetic aberration. Selumetinib is an oral mitogen-activated protein kinase (MEK) 1/2 inhibitor with promising efficacy and good tolerability on relapsed/refractory pLGG. METHODS From January 2021 to January 2024 three patients with refractory OPH-pLGG with KIIA1549-BRAF fusion were treated with Selumetinib 25 mg/sqm/day (compassionate use) all after two lines of chemotherapy. They were males, mean age at diagnosis 8 months, at starting Selumetinib 74 months. All had partial surgery at diagnosis and two of them other debulking surgeries during the treatment. All patients had numerous events of hydrocefalous with need of shunt revision. RESULTS Two patients experienced grade-3 stomatitis, one grade 3 nausea-vomiting, one grade 3 gastritis, one grade 1 increased level of CPK (CTCAE-V5.0). For grade 3 toxicity Selumetinib had to be stopped for a maximum of 7 days with clinical benefit. Two of them have completed treatment with Selumetinib, one is ongoing after 20 months, all with radiological stable disease at MRI. Median time of treatment is 26 months (range 20-30 months). All three experienced a trend in reduction of emergency room admission for ventricular-shunt problems. Median PFS at starting Selumetinib was 62 months, median OS is 97 months. CONCLUSIONS Selumetinib has a good profile of toxicity, allowing a good quality of life procrastinating radiotherapy and reducing surgery events in a context of heavily pretreated relapsed/refractory patients. Further data are needed on both visual and auxological parameters and late side effects.