An international phase 3 clinical trial has demonstrated that selumetinib can significantly reduce tumor size and pain in adults with neurofibromatosis type 1 (NF1), marking the first effective pharmacological treatment for this rare genetic condition in the adult population. The KOMET study, published in The Lancet, represents a breakthrough for patients who previously had limited treatment options beyond complex surgical procedures.
First Pharmacological Treatment for Adult NF1 Patients
The randomized, double-blind trial conducted between 2021 and 2024 included 145 adult participants from around the world with NF1 and symptomatic, inoperable plexiform neurofibromas. Results showed that one in five adults treated with selumetinib experienced significant tumor reduction, accompanied by rapid pain decrease and reduced need for analgesics.
"This represents an important step forward, as it opens the door to being able to treat the various manifestations of this disease pharmacologically," said Ignacio Blanco, lead researcher of the Clinical Genomics Unit at the Germans Trias i Pujol Research Institute (IGTP). "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."
Addressing a Significant Unmet Medical Need
Neurofibromatosis type 1 affects approximately one in every 3,000 people, making it one of the most common rare diseases. The condition manifests through the growth of tumors on nerves called plexiform neurofibromas, which, while benign, are typically painful and often severely disfiguring. These tumors can grow to enormous sizes and cause serious cosmetic and functional impairment.
Prior to this study, adult NF1 patients could only resort to surgery to alleviate disease effects, and surgical intervention was not always feasible due to complexity and associated risks. The intimate integration of tumors with nerves and their tendency to grow in network-like patterns often made surgical treatment unsatisfactory.
Innovative Trial Design Maximizes Patient Access
The KOMET trial featured an innovative design element that distinguished it from conventional placebo-controlled studies. Participants who initially received placebo could access selumetinib under specific conditions: if their tumor progressed or after completing 12 of the 28 planned treatment cycles. This approach allowed researchers to assess drug effectiveness in both patients treated from the outset and those who received treatment later in the study period.
"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," highlighted Blanco, who also serves as head of Expert Clinical Units and Centres, Services and Reference Units (CSUR) at Germans Trias Hospital.
Clinical Significance and Disease Context
While selumetinib is already approved for use in children with NF1, this study represents the first phase 3 trial to evaluate its efficacy and safety specifically in adults. The research addresses a critical gap in treatment options for adult patients with this complex genetic condition.
Neurofibromatoses involve both dermatological and neurological clinical manifestations. The disease often presents with skin manifestations, but neurological symptoms can be predominant or exclusive. The most significant manifestations are tumors that form along nerves, particularly in cutaneous nerve fibers, giving the disease its name: neurofibromatosis, referring to fibrous tissue in the nerves.
Although these tumors rarely become malignant and remain benign throughout life, they can cause substantial morbidity through pain, disfigurement, and functional impairment. The condition can also affect other organs, including the skeleton, particularly the axial skeleton comprising the spine and skull, though this occurs less frequently.
