An international study validates the efficacy of a drug in adults with neurofibromatosis type 1

• This is a rare genetic disease that causes tumour growth and is currently only addressed with palliative surgery.
• A clinical trial involving the Germans Trias i Pujol Research Institute and Hospital demonstrates that administering selumetinib reduces the tumour and the associated pain.

An international study has shown that a drug called selumetinib can reduce the pain and size of tumours caused in adults by neurofibromatosis type 1 (NF1), a rare genetic disease for which there is currently no effective pharmacological treatment.

Although the use of this medicine is approved in children, there had not yet been a phase 3 trial in adults to evaluate its efficacy and safety. This study is the first to demonstrate the effectiveness of a treatment in this population, which until now could only resort to surgery - and not always, due to its complexity and associated risks - to alleviate the effects of the disease.

With an incidence of 1 in every 3,000 people, neurofibromatosis type 1 is one of the most common rare diseases. One of its multiple manifestations is the growth, in one or several parts of the body, of tumours on the nerves called plexiform neurofibromas. Although benign, they are usually painful and often very disfiguring.

The study, called KOMET and published in The Lancet, has shown that in 1 in every 5 adults with plexiform neurofibromas treated with selumetinib, there was a significant reduction in the tumour. A rapid decrease in pain and a reduced need for analgesics were also observed.

For Ignacio Blanco, lead researcher of the Clinical Genomics Unit at the Germans Trias i Pujol Research Institute (IGTP), all of this "represents an important step forward, as it opens the door to being able to treat the various manifestations of this disease pharmacologically." He adds: "Until now, we had very few options for these patients. Now we could offer them a drug that would first reduce the tumour and then allow us to operate."

The drug was made available to all participants

The randomised, double-blind trial was conducted between 2021 and 2024 and included 145 adult participants from around the world with NF1 and symptomatic, inoperable plexiform neurofibromas. One of the innovative features of its design was that participants who initially received a placebo could also access selumetinib under certain conditions: if the tumour progressed or if they completed 12 of the 28 planned treatment cycles. This allowed the effectiveness of the drug to be assessed both in patients treated from the outset and in those who received it later.

"We were therefore able to compare and assess the drug's effectiveness in reducing the tumour and the associated pain, both in patients who received it from day one and in those who started it a few months later," highlights Blanco, who is also head of Expert Clinical Units and of Centres, Services and Reference Units (CSUR) at Germans Trias Hospital.

In this regard, the participation of Germans Trias in this trial is explained by its international leadership in this field, as it is a CSUR of the National Health System for adult patients with genetic neurocutaneous syndromes. Also known as phakomatoses, these are a group of hereditary diseases - including NF1 - that are characterised by the presence of tumours in various parts of the body, potentially affecting the nervous system, eyes, and skin.

Generally benign but painful

Neurofibromatoses therefore involve dermatological and neurological clinical signs. The disease often presents only skin manifestations, but neurological manifestations can also be predominant or exclusive. The most important of these are tumours that form along the nerves, especially in the cutaneous nerve fibres - hence the name of the disease: neurofibromatosis, or fibrous tissue in the nerves.

Although these tumours rarely become malignant and are therefore considered benign throughout life, they can grow to enormous sizes and cause serious disfigurement. In addition, surgical treatment is often unsatisfactory due to the intimate integration with the nerves and the tendency of some tumours to grow in a network-like fashion.

Moreover, neurofibromatoses can also, although far less frequently, affect other organs in the body, such as the skeleton - particularly the axial skeleton (spine and skull).