CNS Drugs. 2026 Jul 17. doi: 10.1007/s40263-026-01316-6. Online ahead of print.
ABSTRACT
BACKGROUND: Plexiform neurofibromas (PN) represent a significant cause of morbidity among patients diagnosed with neurofibromatosis type 1 (NF1). MEK inhibitors continue to be developed as targeted therapies by inhibiting the mitogen-activated protein kinase pathway to treat PN; nonetheless to this day, therapeutic responses have varied across different patient populations and clinical contexts, and the overall efficacy and tolerability of these agents remain incompletely characterized.
OBJECTIVE: We aimed to systematically evaluate the efficacy and safety of MEK inhibitor therapy in patients with NF1-associated PN and to evaluate differences among key subgroups based on the most contemporary metadata.
METHODS: A comprehensive search was performed across electronic databases to identify studies that reported outcomes related to MEK inhibitor therapy in NF1-associated PN. Pooled proportions were calculated using a random-effects meta-analysis with logit transformation. Outcomes assessed included objective response rate, disease control rate, disease progression rate, and grade ≥ 3 adverse events.
RESULTS: A total of 23 studies comprising 769 patients were included. The pooled objective response rate was estimated at 56% (95% confidence interval [CI] 46-65; I2 = 79.2%), with significantly higher response rates observed in clinical trials (61%) compared with real-world cohorts (44%) [p = 0.035], while no statistically significant difference was observed between pediatric (58%) versus adult populations (51%) [p = 0.407]. The pooled disease control rate was 96% (95% CI 91-98; I2 = 17%) and the pooled disease progression rate was estimated at 2% (95% CI 1-5; I2 = 0%), both reflecting on-treatment outcomes. Grade ≥ 3 adverse events occurred in 13% of patients (95% CI 6-25; I2 = 51.9%). Subgroup analyses revealed comparable disease control across study settings, with moderate variability in response and toxicity estimates.
CONCLUSIONS: The use of MEK inhibitors is associated with high rates of disease control and minimal tumor progression in patients with NF1-related PN, with consistent effects observed across clinical trial and real-world environments. Although tumor reduction occurs in some patients, the predominant therapeutic benefit appears to be sustained disease stabilization, with response variability noted among different age groups and study designs.
PMID:42467350 | DOI:10.1007/s40263-026-01316-6
