Plexiform Neurofibromas: Discovery, Translational Research & Clinical Trials

In 2020 the first-ever drug for plexiform neurofibromas - or any NF1 manifestation – received FDA approval. NTAP was at the forefront of this effort through our funding and leadership.

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Plexiform neurofibroma tumors research and clinical trials






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Plexiform Neurofibromas: State of the Field

Plexiform neurofibroma (pNF) symptoms

Plexiform neurofibromas (pNFs) are histologically benign tumors that grow along individual nerves or a collection of peripheral nerves. They are part of a class of tumor called peripheral nerve sheath tumors and are associated with pain, weakness, sensory changes, disfigurement, loss of vital function (vision, hearing, airway, bladder) and in a subset of people, conversion to an aggressive malignancy called malignant peripheral nerve sheath tumor (MPNST).

pNFs are a common tumor in individuals with NF1, a genetic disorder characterized by distinctive skin abnormalities and a high number of both benign and malignant tumors that grow throughout the body. pNFs can occur in any part of the body and can cause disfiguring, significant disability or death. In 2020, the first therapy was approved by the Food and Drug Administration for the treatment of unresectable pNFs in children with NF1 based on the remarkable results in the study. While this is a major advancement for the field that has altered clinical practice and outcomes for people with NF1, much more work is needed to determine if there are dosing schedules or different drugs that will prevent pNF growth and development of pNF associated morbidity, prevent conversion to malignancy and can be well tolerated for years of treatment.

The current strategy for clinical management of pNFs is observation. While many pNFs remain stable over an individuals’ lifetime, a significant portion progress clinically and radiographically. For patients with symptomatic or threatening pNFs that require treatment, surgery remains the standard of care. However, because pNF tumors grow within nerve, they are almost never amenable to complete surgical resection and in many cases surgery is not feasible without significant morbidity due to the location of the tumor relative to other vital organs. Partial removal or debulking that maintains some of the normal nerve fibers is generally possible, but is often of limited utility as these tumors tend to regrow. Furthermore, with each surgery, there is increased risk of permanent nerve damage.

Radiation therapy is reserved for patients with proven malignancy and plays a very limited role in the management of pNF tumors.

Selumetinib is approved for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable pNFs. Other MEK inhibitors including binimetinib, mirdametinib, trametinib and the multi-kinase inhibitor cabozantinib have also showed benefit in clinical trials for pNFs in adults or pediatric populations. Combination therapy studies are in development to improve the overall response rate, durability of response, depth of response and to improve the tolerability of long term targeted therapy. Ongoing challenges are identification of individualized treatment schedules (including necessary duration of treatment in adults and pediatric populations), long-term safety monitoring of MEK inhibitors, strategies to prevent pNF growth in children and new targets for tumors that are non-responsive to current drug therapies.