Comparative Efficacy of MEK Inhibitors in Neurofibromatosis Type One–Associated Plexiform Neurofibromas: A Network Meta-analysis
Meghnath Kakde1, Shradha Kakde2, Purvi Kaurani3, Anushka Upadhyay4, Harshawardhan Ramteke5, Rakhshanda Khan6
1smt.kashibai navale medical college and general hospital, 2MGM medical college and hospital, 3DY Patil University School of Medicine, 4jinzhou medical university, 5Anhui medical university, 6Ayaan Institute of medical sciences
Objective:

To compare the efficacy and safety of currently available MEK inhibitors—selumetinib, mirdametinib, trametinib, and binimetinib—in children and adults with neurofibromatosis type 1 (NF1)–associated symptomatic, inoperable plexiform neurofibromas (PN).

Background:
NF1 is a RASopathy with overactive RAS/RAF/MEK/ERK signaling causing progressive plexiform neurofibromas. MEK inhibitors are the first effective systemic therapy. Selumetinib was approved for pediatric NF1-PN, and mirdametinib received FDA approval in 2025 for both adults and children. This network meta-analysis compares the efficacy and safety of available MEK inhibitors to define their relative clinical performance
Design/Methods:

We searched PubMed, Embase, and clinical-trial registries for studies on MEK inhibitors in NF1-associated PN, extracted efficacy and safety data, assessed risk of bias using the ROB 2.0 tool, and performed a Bayesian network meta-analysis to estimate pooled ORs and SUCRA rankings for ≥20% tumor volume reduction.

Results:

Seven trials encompassing 843 patients (mean age 12.8 ± 7.1 years; mean follow-up 24.5 months) were analyzed: selumetinib (n = 355), mirdametinib (n = 254), trametinib (n = 146), and binimetinib (n = 88). Pooled response rates ranged from 46–71 %, with significant inter-agent variation (p < 0.001). Relative to best supportive care, pooled ORs (95 % CI) for partial response were: Selumetinib 12.4 (6.3–24.6); Mirdametinib 9.6 (4.8–19.3); Binimetinib 7.8 (3.1–15.9); Trametinib 5.2 (2.4–11.4). SUCRA ranking favored selumetinib (0.93) > mirdametinib (0.84) > binimetinib (0.69) > trametinib (0.54). Mean volumetric reduction reached –31 % with selumetinib and –28 % with mirdametinib. Common adverse events included acneiform rash (41 %), diarrhea (34 %), elevated CPK (18 %), and asymptomatic LVEF decline (6 %); < 8 % discontinued due to toxicity.


Conclusions:

MEK inhibition provides durable tumor regression in NF1-PN, with selumetinib showing the highest efficacy and mirdametinib comparable adult benefit; overall evidence quality was moderate with low risk of bias

10.1212/WNL.0000000000216782
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