A phase 2 study of trametinib for patients with pediatric glioma or plexiform neurofibroma with refractory tumor and activation of the MAPK/ERK pathway.

Abstract

2042 Background: Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children and the majority of PLGG have activation of the MAPK/ERK pathway. Plexiform neurofibromas (PN) are found in up to 50% of patients with neurofibromatosis type 1 (NF1). Trametinib has been used widely to treat PLGG and PN, but no clinical trial has reported its efficacy. Methods: This multicenter phase II trial includes patients aged ≥ 1 month to ≤ 25 years with progressing/refractory PLGG groups or PN. The primary objective was to evaluate the overall response rate after daily oral trametinib administration for eighteen 28-day cycles. Results: As of January 31st, 2022, 60 patients with PLGG and 45 patients with PN have been enrolled. Median age is 9.5 years (range 1.8-25.4) for PLGG and 11 years (range 0.7-19.8) for PN. Median follow-up is 18 months (range 0.1-38.1). Fifty-three patients with PLGG were evaluable. The overall response includes: 1 complete response (CR) (1.9%), 7 partial response PR (13.2%), 17 minor response MR (32.1%), 23 stable disease (SD) (43.4%) and 5 progressive disease (PD) (9.4%). Twenty-eight patients with a total of 32 PN were available for volumetric analysis. Volumetric assessment demonstrated an overall response rate of 60.7% compared to 24.1% when using RECIST 1.1 and 62.5% of PN showed a decrease of more than 20% in volume. Median volume change was a decrease of 30% (range -93.5 to 14.3). A total of 59 (69.4%) patients discontinued treatment as planned after 18 cycles and 9 (10.6%) patients had to stop trametinib due to adverse events. Conclusions: Response rates observed in our study suggest that trametinib is a potentially effective targeted therapy for patients with recurrent/refractory PLGG and PN. Treatment was overall well tolerated. This trial will continue to gather data on duration of response and long-term outcome for PLGG and PN treated with trametinib. Clinical trial information: NCT03363217.