An evaluation of selumetinib for the treatment of neurofibromatosis type 1-associated symptomatic, inoperable plexiform neurofibromas

ABSTRACT Introduction: Plexiform neurofibromas (PNs) are present in up to half of patients with neurofibromatosis type 1 (NF1). PNs consist of a proliferation of abnormal cells in the nerve sheath and can lead to significant comorbidities. Most PNs are diagnosed in early childhood when the most rapid growth rate generally occurs. Historically there has been a paucity of effective treatment options for patients with PNs, with surgery being the standard of care. As knowledge has increased regarding the NF1 gene and the function of its protein product neurofibromin, therapies targeting the Ras signaling pathway have been tested, first in preclinical models and subsequently in clinical trials. Areas covered: This review focuses on selumetinib (KOSELUGOTM; AZD6244, ARRY-142,886) and the management of PNs. A literature search was undertaken using PubMed with keywords ‘neurofibromatosis,’ ‘plexiform neurofibromas,’ ‘selumetinib,’ and ‘MEK inhibitor.’ Expert opinion: Selumetinib is the first FDA approved drug for the treatment of PNs. Prior to its development, options for patients with PNs causing morbidity were limited. Surgical intervention can be difficult, debilitating, and often futile. With the efficacy seen in the phase 1 and 2 trials for patients with NF1-associated PNs, the outlook has become one of the hope and excitement.