UNDERSTANDING COMMONLY REPORTED (≥15%) TREATMENT-RELATED ADVERSE EVENTS IN THE RENEU TRIAL OF MIRDAMETINIB IN CHILDREN AND ADULTS WITH NEUROFIBROMATOSIS TYPE 1 (NF1)-ASSOCIATED PLEXIFORM NEUROFIBROMA (PN)

Document Type

Conference Proceeding

Publication Date

11-11-2025

Publication Title

Neuro Oncol

Keywords

dermatitis, diarrhea, adult, child, drug approval, nausea, plexiform neurofibroma, neurofibromatosis 1, paronychia, vomiting, ejection fraction, older adult, cardiac troponin i, adverse event, mirdametinib

Abstract

BACKGROUND: Mirdametinib is the first FDA-approved MEK1/2 inhibitor for both adults and children ( ≥ 2y) with symptomatic NF1-PN. In ReNeu, symptomatic improvement and PN volume reductions were observed at the earliest assessments (~91 and ~152 days, respectively) and were sustained. This analysis evaluated time to first onset and resolution of commonly reported TRAEs in the ReNeu trial. METHODS: Data cutoff (DCO) was September 20, 2023. Median time to first onset and resolution (days) for common TRAEs ( ≥ 15%) were evaluated for prepubescents ( ≥ 2 to <12y, n=32), postpubescents ( ≥ 12 to <18y, n=24), younger adults ( ≥ 18 to ≤ 50y, n=48), and older adults (>50y, n=10). RESULTS: Common TRAEs were mostly grades 1 to 2 (83%). In prepubescents, median day (range) of onset was 32 (14, 263) for vomiting, 71 (19, 386) for dermatitis acneiform, 123 (1, 663) for diarrhea, 124 (52, 775) for paronychia, and 127 (2, 663) for nausea. For postpubescents, median day (range) of onset was 8 (1, 438) for diarrhea, 8 (2, 574) for nausea, 12 (1, 252) for dermatitis acneiform, 28 (2, 354) for vomiting, and 110 (43, 245) for paronychia. In younger adults, median day (range) of onset was 5 (1, 352) for nausea, 8 (2, 15) for dermatitis acneiform, 9 (2, 73) for diarrhea, and 29 (1, 264) for vomiting. For older adults, median day (range) of onset was 4 (1, 286) for diarrhea, 9 (2, 15) for nausea, and 13 (2, 38) for dermatitis acneiform. Time to resolution was variable between TRAEs and among patients in all age groups; 90% resolved completely by DCO. Among all patients, 18 had a TRAE of asymptomatic ejection fraction decrease, with all but one resolving by DCO. CONCLUSIONS: Overall, common TRAEs arose before treatment benefits and were generally resoluble by DCO. Proactively managing TRAEs may improve treatment experience and adherence.

Volume

27

Issue

Supplement_5

First Page

v125

Last Page

v126

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