Natural History and Disease Burden of Neurofibromatosis Type 1 with Plexiform Neurofibromas: A Systematic Literature Review

Abstract

Neurofibromatosis type 1 (NF1) is an incurable genetic condition that frequently includes the development of plexiform neurofibromas (PNs) in patients. A systematic literature review was conducted to identify data on the natural history, disease burden, and treatment patterns among patients diagnosed with NF1 and PN, as well as to identify evidence gaps in these areas. MEDLINE and MEDLINE In-Process, Embase, and Cochrane Library Searches were searched using predefined terms. Potential references underwent two phases of screening by two independent researchers. A total of 39 references focusing on populations of patients with both NF1 and PN were included in this review. The wide range of PN-related complications creates a substantial quality-of-life (QOL) burden for patients, including pain, social functioning, physical function impact, stigma, and emotional distress. The severe burden of NF1 with PN on the QOL of patients demonstrates the high unmet need for an effective treatment option that can reduce tumor burden and improve QOL. The heterogeneity of measurement tools used to evaluate QOL and the gap in data evaluating the health economic burden of PN should be the focus of future research.

A Review of Selumetinib in the Treatment of Neurofibromatosis Type 1–Related Plexiform Neurofibromas

“…Several targeted agents have been evaluated to ameliorate RAS hyperactivation and tumorigenesis in NF1, but the agents specifically targeting MEK/ERK have shown the most promise. 8…”

“…Several targeted agents have been evaluated to ameliorate RAS hyperactivation and tumorigenesis in NF1, but the agents specifically targeting MEK/ERK have shown the most promise. 8 MEK 1 and 2 are homologues and upstream regulators of the ERK pathway responsible for activating cyclin D1 and subsequent cell proliferation. Selumetinib-a potent, selective, oral, ATP noncompetitive small-molecule inhibitor of both MEK 1 and 2 phosphorylation-binds to the MEK 1/2 proteins, resulting in conformational changes, cell signal transduction disruption, and arrest of tumor cell growth and proliferation.…”

“…6 Over the past 20 years, clinical studies evaluating imatinib, sirolimus, tipifarnib, pirfenidone, peginterferon, trametinib, cabozantinib, and selumetinib have been conducted in NF1-associated PN; however, until recently, no US Food and Drug Administration (FDA)-approved pharmacological option existed. [8][9][10][11][12][13][14][15][16] To date, selumetinib has demonstrated therapeutic activity and treatment potential for patients with this challenging and unmet medical need. 8 Selumetinib (Koselugo; ARRY-142886, AZD6244), an oral MEK-1/2 inhibitor, was approved on April 10, 2020, by the FDA for symptomatic, inoperable PNs in pediatric patients 2 years and older with NF1.…”

“…[8][9][10][11][12][13][14][15][16] To date, selumetinib has demonstrated therapeutic activity and treatment potential for patients with this challenging and unmet medical need. 8 Selumetinib (Koselugo; ARRY-142886, AZD6244), an oral MEK-1/2 inhibitor, was approved on April 10, 2020, by the FDA for symptomatic, inoperable PNs in pediatric patients 2 years and older with NF1. 17 The aim of this article is to review the safety and efficacy of selumetinib for treating PNs in patients with NF1.…”

Adolescents and young adults with neurofibromatosis type 1: A descriptive study of adaptive functioning

“…These worries prevented people from participating in public activities due to reluctance to leave the house (Heaney et al, 2019). In a recent systematic review, the authors concluded that a range of pNF‐related sequelae, including impaired social functioning and emotional distress, have a negative impact on quality of life (Copley‐Merriman et al, 2021).…”