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).

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.

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.

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