Abstract Background Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children. The majority of PLGG have activation of the MAPK/ERK pathway. Methods This phase II trial includes three recurrent/refractory PLGG groups: NF1 PLGG, KIAA1549-BRAF fusion PLGG and PLGG with other MAPK/ERK pathway activation (excluding BRAF V600E). Treatment phase has been completed by all patients with PLGG. The primary objective was to evaluate the overall response rate based on modified RANO criteria after daily oral trametinib administration for 18 cycles, each cycle lasting 28 days. Results As of November 05, 2024 recruitment was completed with 68 PLGG patients enrolled (NF1: n = 12; KIAA1549-BRAF fusion: n = 42; other: n = 14 including 7 patients with FGFR alterations). Median age at enrollment was 9.2 years (range 1.8-25.4). Median follow-up was 39.5 months (range 0.9-57.2).Sixty-five patients were evaluable to assess response. The overall best responses include: 1 complete response (1.5%), 12 partial response (PR) (18.2%), 17 minor response (MR) (25.8%), 33 stable disease (50%), 3 progressive disease (4.6%). Median time to response was 2.8 months (range 2.4-13.6) with a median duration of response of 23.8 months (range 0-49.9). Treatment was discontinued for 68 patients: including 41 (60.3%) after completing 18 cycles as planned, 8 (11.8%) for progressive disease and 7 (10.3%) for adverse events. Median progression-free (PFS) survival was 33.3 months (95% CI 23.0-48.8), 18 months PFS was 73.2 % (95% CI 23.0-48.8) and the 36 months PFS was 45.5 % (95% CI 38.5-52.5). Fourteen (20.6%) patients progressed after discontinuation of treatment at a median time of 7.4 months (0.1-18 months). Eighteen patients restarted treatment after discontinuation. Median time to restart treatment was 16.3 months (range 2.1-41.7) Conclusion Trametinib can be an effective and well tolerated therapy for patients with recurrent/refractory PLGG
Perreault et al. (Tue,) studied this question.