Observational Study to Evaluate the Effect and Safety of Selumetinib in Pediatric Patients With NF1-PNs

Neurofibromatosis type 1 (NF1) is a rare and incurable autosomal dominant genetic disorder that is characterized by manifestations in multiple organ systems including tumors of the nervous system. Although NF1 is inherited via autosomal dominance, 50% of detected mutations are de novo. The population prevalence of NF1 estimates ranging from approximately 1/2000 to 1/4000 , and there are estimated 460,000 patients in China. The condition is usually recognized in early childhood, when pigmentary manifestations emerge. NF1 patients have decreased life expectancy of 15 years compared to the general population. High-grade glioma (HGG) and malignant peripheral nerve sheath tumor (MPNST) were noteworthy causes of death among patients with NF1.

Plexiform neurofibromas (PN) are tumors arise from Schwann cells of peripheral, visceral, or subcutaneous nerves, affecting 30%-50% of patients with NF1. PN can cause substantial complications including pain, functional impairment, disfigurement and have a risk of malignant transformation. The lifetime incidence of MPNST in patients with NF1 is 8%-13% , and the presence of a PN elevates the risk of MPNST formation by 20-fold among NF1 patients. Most PN are diagnosed in early childhood and grow most rapidly during this period. Surgical resection is the mainstay treatment for PN, yet surgical treatment does not have satisfactory effect. Complete surgical resection of these tumors is often infeasible due to the extensive growth of the tumor and invasion of surrounding tissues, and partial removal often comes with a high recurrence rate. Conventional chemotherapy and radiotherapy have shown limited efficacy for NF1-associated PN. As a result, medical therapies targeting PN have been evaluated in clinical trials.

The therapeutic revolution came in 2020 with the approval of selumetinib for pediatric patients with NF1-associated PN. Selumetinib is an oral selective inhibitor of MEK 1 and 2 and has been confirmed effective for NF1-associated PN in SPRINT Phase II Stratum 1. The overall response rate was 68% (34/50), and 82% (28/34) of these patients had a durable response (lasting ≥12 months) (Gross AM et al, 2020). Selumetinib was approved by the United States Food and Drug Administration (US-FDA) on April 10, 2020, becoming the first approved targeted therapy for pediatric patients with NF1-associated PN. On April 28, 2023, the China National Medical Products Administration (NMPA) approved selumetinib for pediatric patients aged 3 years and older diagnosed with NF1 who have symptomatic, inoperable PN.

To date, evidence on real-world data of clinical benefit of selumetinib for NF1-associated PN patients among Chinese population is lacking. Moreover, due to the relatively rare affected population, disease knowledge of NF1 and PN is limited among healthcare professionals (HCPs) and throughout the society. An observational study of pediatric patients with NF1-associated PN treated with selumetinib in China will fulfill the data gap of effectiveness and safety of selumetinib for Chinese NF1-PN patients and will facilitate the understanding of disease characteristics and treatment in this population in a real-world setting.