Abstract
BACKGROUND: Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children. It is now known that the majority of PLGG have activation of the MAPK/ERK pathway. We hypothesize that we will observe responses in recurrent/refractory PLGG treated with trametinib. METHODS: This is a multicenter phase II including three progressing/refractory PLGG groups: NF1 patients, KIAA1549-BRAF fusion patients and patients with other activation of the MAPK/ERK pathway (excluding V600E). Patients will receive daily oral trametinib for a total of 18 cycles of 28 days. A total of 104 patients will be enrolled in seven Canadian centers. Secondary objectives include the assessment of progression-free survival, tolerability of trametinib, serum levels of trametinib and evaluation of quality of life during treatment. RESULTS: As of January 7 2020, 28 patients have been enrolled (NF1: 6 patients, KIAA1549-BRAF fusion: 17, other: 5 including 3 patients FGFR1 alteration). Median age is 8.5 years (range 2.5–25.4 years). Median follow-up is currently 4.6 months (range 0.16–14.7 months). Twenty patients are currently evaluable. Best response includes: 1 complete response (5%), 3 partial response (15%), 4 minor response (20%), 8 stable disease (40%), 4 progressive disease (20%). 8 patients (28,5%) discontinued treatment: 4 for progressive disease, 3 adverse event (alanine aminotransferase increase), 1 withdrew. CONCLUSION: Trametinib is potential effective targeted therapy for patients with recurrent/refractory PLGG. Overall treatment is well tolerated. This ongoing trial will continue to gather data on response rate, duration of response and safety of trametinib for PLGG.