Selumetinib safe option for treatment of inoperable plexiform neurofibromas

Selumetinib is a medication that is both effective and safe for young patients having symptomatic, inoperable plexiform neurofibromas, says an article published in Neurology.

AstraZeneca is developing selumetinib, a mitogen-activated protein kinase 1 and 2 (MEK1/2) inhibitor, for the treatment of tumors associated with neurofibromatosis and other malignancies. Even though the current approval of selumetinib is anticipated to reshape the planning of children with neurofibromatosis type 1 (NF1), especially those with symptomatic and inoperable plexiform neurofibromas, no critical appraisal based on the most recent studies has summarized its efficacy and safety. As a result, Jisun Hwang and colleagues undertook this research to examine the effectiveness and safety of selumetinib in children with NF1.

Up until January 28, 2021, original studies documenting the effectiveness and safety of selumetinib in patients with NF1 were found in PubMed and EMBASE. The DerSimonian–Laird technique based on random-effects modeling was used to compute the pooled objective response rates (ORRs) and disease control rates (DCRs). The proportion of adverse events (AEs) that were pooled was also computed. The evidence's quality was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.

The key findings of this study were as follow:

1. Our analysis includes five trials with a total of 126 individuals.

2. The studies' evidence quality ranged from extremely poor to moderate.

3. The pooled ORR was 73.8% (95% confidence interval: 57.3%–85.5%), and the DCR was 92.5% (95% confidence interval: 66.5%–98.7%).

4. The two most prevalent adverse events (AEs) were diarrhea (63.8%, 95% CI 52.9% –73.4%) and an increase in creatine kinase levels (63.3%, 95% CI 35.6% –84.3%).

In conclusion, this study's findings clearly demonstrate the efficacy of selumetinib in symptomatic inoperable plexiform neurofibromas ; nevertheless, larger-scale randomized controlled trials are required to determine the long-term outcome of patients administered with this medicine.

Reference:

Hwang, J., Yoon, H. M., Lee, B. H., Kim, P. H., & Kim, K. W. (2022). Efficacy and Safety of Selumetinib in Pediatric Patients With Neurofibromatosis Type 1. In Neurology (Vol. 98, Issue 9, pp. e938–e946). Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1212/wnl.0000000000013296