LGG-12. TRAMETINIB FOR THE TREATMENT OF RECURRENT/PROGRESSIVE PEDIATRIC LOW GRADE GLIOMA: A SINGLE INSTITUTION EXPERIENCE

INTRODUCTION: Pediatric low-grade gliomas (pLGGs) are the most common CNS tumor of childhood and comprise a heterogenous group of tumors. Children with progressive pLGG typically require numerous regimens of therapy including surgical resection, chemotherapy and rarely, radiation therapy. The presence of frequent genetic alterations activating the mitogen-activated-protein-kinase (MAPK) signaling pathway has recently led to a more targeted therapeutic approach. We describe our institutional experience using trametinib, an FDA-approved MEK inhibitor for recurrent/progressive pLGGs. METHODS: We performed a retrospective, IRB approved, chart review of all patients with recurrent/progressive pLGGs treated with trametinib off-study at Dana-Farber / Boston’s Children’s Cancer and Blood Disorder Center between 2016–2018. RESULTS: Eleven patients were identified, with ten evaluable for response. Median age at commencement of trametinib treatment was 14.7 years old (range 7.3–25.9 years; 6 male: 5 female). Molecular status included KIAA 1549-BRAF fusion (n=3), NF1 (n=4), FGFR mutation and heterozygous CDKN2A loss (n=1 each), unknown mutational status (n=2). Median number of prior treatment regimens was 5 (range 1–7). Median duration on treatment with trametinib was 13.4 months (range 1.5–24.8 months). Based on RANO criteria, responses included partial (n=1), minor response (n=1) and stable disease (n=5) as best response. Four patients remain on therapy with trametinib (range 1.5–24.8 months) with two patients having discontinued therapy secondary to disease progression. The most common toxicities were skin rash, fatigue and gastrointestinal disturbance. Five patients required dose reduction for toxicities. Two patients experienced intracranial hemorrhage (ICH) while on trametinib (at 5 and 498 days). While it is unclear whether ICH was directly attributable to trametinib, therapy was discontinued. CONCLUSION: Trametinib appears to be an effective treatment for patients with recurrent/progressive pLGG. The toxicities of this therapy warrant further investigation, particularly the potential risk for intracranial hemorrhage. Early phase clinical trials are underway.