CUTANEOUS neurofibromas (cNFs) are a common manifestation of neurofibromatosis type 1 (NF1), often causing itching, disfigurement, pain, and emotional distress. This study aimed to assess the impact of selumetinib, a mitogen-activated protein kinase kinase (MEK) inhibitor, on cNFs, focusing on changes in tumour volume and patient-reported outcomes.
Conducted at the National Cancer Institute and the University of Alabama at Birmingham, USA, this nonrandomised pilot trial enrolled adults with NF1 who had at least nine measurable cNFs. The study ran from August 2017 to August 2023. Participants received selumetinib for up to 24 cycles, each lasting 28 days, with tumour assessments performed after every four cycles. Tumour volume and number were measured using calipers and photography, while the Skindex-29 Quality of Life assessment evaluated symptoms, emotional impact, function, itching, and pain.
Among the 11 participants, the median age was 54 years (range: 28–75), and six were female. The median reduction in cNF volume was 28.5% (interquartile range: −40.9% to −12.5%), with some participants demonstrating a visible reduction in tumour burden. However, only four participants completed all 24 treatment cycles, with two continuing beyond the study due to perceived clinical benefit. The treatment was associated with reversible drug-related adverse events, most commonly dermatologic reactions such as dry skin and rash. Two participants discontinued treatment due to concerns about a severe drug reaction with eosinophilia and systemic symptoms.
Although the Skindex-29 assessment indicated an improvement in emotional well-being after the first cycle, there were no significant or lasting changes in other patient-reported outcomes. Study enrollment was hindered by the COVID-19 pandemic, highlighting the challenges in conducting clinical trials for cNF treatments. The frequent occurrence of dermatologic adverse events further complicates the use of selumetinib in this patient population.
While this study demonstrated a measurable reduction in cNF volume, the lack of sustained improvement in patient-reported outcomes suggests that alternative therapeutic approaches may be needed. Future larger-scale studies incorporating advanced imaging techniques, such as three-dimensional photography, could provide more comprehensive and generalisable findings for the diverse NF1 population.
Katie Wright, EMJ
Reference
Gross AM et al. treatment of cutaneous neurofibromas in neurofibromatosis Type 1 with MEK inhibitor selumetinib: a nonrandomized clinical trial. JAMA Dermatol. 2025;DOI:10.1001/jamadermatol.2024.6574.
