MEK inhibitors shrank about half of inoperable NF1 plexiform neurofibromas

Design

Systematic review and meta-analysis of single-arm and randomised studies

Population

9 studies, 528 children and adults with symptomatic inoperable NF1 plexiform neurofibromas

Primary outcome

Objective response (≥20% volume reduction)

Effect

53.7% (95% CI 40.5% to 66.6%); children 62.9%, adults 40.8%

This meta-analysis pooled nine studies (528 participants) of MEK inhibitor monotherapy (selumetinib, mirdametinib, trametinib and binimetinib) for symptomatic, inoperable plexiform neurofibromas in neurofibromatosis type 1.

The pooled response rate (at least 20% volume reduction) was 53.7% (95% CI 40.5% to 66.6%), higher in children (62.9%) than adults (40.8%), with high heterogeneity. Eight of nine strata were single-arm, so these are descriptive proportions. The one randomised trial, KOMET in adults, reported 20% response with treatment against 5% with placebo. Responses were partial but usually durable, with improvements in pain and quality of life. Toxicity was mostly low grade, with uncommon cardiac and ocular events.

Benefit depends on continued treatment, and effects on malignant transformation are unknown. For patients with symptomatic inoperable tumours, MEK inhibition is now a supported option, with cardiac and eye monitoring.

• Consider referral for MEK inhibitor treatment in symptomatic, inoperable NF1 plexiform neurofibromas.
• Set expectations: shrinkage is usually partial and depends on continuing treatment.
• Arrange baseline and periodic echocardiography and eye examination on treatment.
• Keep watching for signs of malignant transformation; MEK inhibition is not known to prevent it.

Why it matters

Adults now have an approved option and randomised evidence, where previously the data were paediatric.

Don't overread it

Mostly single-arm evidence across four different drugs; this is not a class effect estimate.

The statistics, in plain English

A pooled response of 53.7% from mostly single-arm studies describes how often tumours shrank, not how much better treatment is than no treatment. I² of 84% means results varied widely, partly by age and partly because of the one randomised trial's stricter design.

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