EANO 2025: Evolving care in NF1-PN

Understanding NF1-PN: What clinicians need to know

Neurofibromatosis type 1 (NF1) is a lifelong, multisystem disorder with a highly variable presentation.¹ For clinicians, this means ongoing complexity across diagnosis, treatment, and care coordination.¹ Even with new treatment options emerging, experts note that challenges persist, from applying diagnostic criteria to addressing the psychosocial burden that continues to affect quality of life.

Care is even more complex in patients with NF1–associated plexiform neurofibromas (NF1-PN), a distinct tumor type that grows along nerve sheaths and is often deep, extensive, and difficult to remove.² While NF1 already demands specialist care, the presence of PN adds another clinical challenge.

Although classed as a rare disease,^3,4 NF1 is more common than many clinicians realize, occurring in approximately 1 in 3,000 people worldwide.⁵ It affects all genders and ethnicities equally, with no known geographic or racial predisposition.⁵ Notably, over half of individuals with NF1 will develop PN, underscoring the importance of early recognition.⁵

NF1 expert Said Farschtschi (University Medical Center Hamburg-Eppendorf, Germany) explains that NF1 isn’t clearly overseen by any one specialty, likely because it affects multiple systems across a patient’s lifetime. This lack of clinical ownership contributes to fragmented care, especially during the transition from pediatric to adult services, where patients are most vulnerable.

Farschtschi notes that the disease evolves with age, with malignant transformation far more common in adults than in children. These age-related shifts, combined with inconsistent care pathways, highlight the need for more effective management strategies.

Innovative care models are needed to strengthen multidisciplinary collaboration and expand access to specialist centers that prioritize continuity of care and patient-specific goals.

Watch an interview with Farschtschi to hear his insights on unmet needs, clinical challenges, and the next steps for advancing NF1 care.

What’s in the NF1-PN armamentarium?

For years, patients and clinicians had few options beyond surgery and watchful waiting, often with limited success. However, the treatment landscape for NF1-PN is beginning to shift.

Two targeted therapies, selumetinib and mirdametinib (both MEK inhibitors), are now approved in the USA and Europe, offering non-surgical options for patients with symptomatic, inoperable tumors. MEK inhibition is particularly relevant in NF1 due to its role in the dysregulated RAS/MAPK pathway.⁶ Selumetinib received U.S. Food and Drug Administration (FDA) approval in April 2020 for children aged 2 years and older, and its indication was recently expanded in September 2025 to include patients as young as 1 year.^7-9

Mirdametinib followed with FDA approval in February 2025 for both adult and pediatric patients aged 2  years and older with conditional marketing authorization.^10,11 These milestones mark a turning point for families who previously had few treatment options.

Yet, Farschtschi points out that treatment advances alone are not enough. NF1 is a complex disorder that often falls outside the radar of non-specialist teams and lacks clear clinical ownership. Structured guidelines are still missing, and care gaps persist, especially during the transition from pediatric to adult care. Farschtschi emphasizes that treatment decisions must go beyond tumor size, balancing long-term feasibility with individual goals and quality of life.

What’s next in NF1-PN care?

Dusica Babovic-Vuksanovic (Mayo Clinic, Rochester, Minnesota, USA) notes how the arrival of targeted therapies such as selumetinib and mirdametinib has changed the outlook for those living with NF1-PN. These MEK inhibitors offer non-surgical treatment options for patients with symptomatic, inoperable tumors, helping to reduce tumor burden. It is a meaningful shift in care, especially for children and families who previously had no viable alternatives.

ReNeu trial: Its clinical impact and patient outcomes

At the 20th Meeting of the European Association of Neuro-Oncology (EANO 2025), Babovic-Vuksanovic presented long-term data from the ReNeu trial, which met its primary endpoints and confirmed mirdametinib’s efficacy. She reported deep and durable responses, with more than 50% tumor volume reduction achieved in 18 adults and 19 children. The confirmed objective response rate reached 55% in pediatric patients and 47% in adults, with some patients responding after just a few cycles and others maintaining benefit even after completing 24 cycles of therapy.

Watch an interview with Babovic-Vuksanovic to hear more about the ReNeu trial and its clinical implications.

Pain – one of the most burdensome symptoms for patients – emerged as the most significant patient-reported outcome. Babovic-Vuksanovic emphasized that pain reduction was both consistent and clinically meaningful across age groups. She also highlighted mirdametinib’s favorable safety profile, with most adverse events being grade 1 or 2, and no new safety signals reported.

In her closing remarks, she underscored the importance of multidisciplinary teamwork, noting that targeted therapies like mirdametinib are reshaping care pathways and improving quality of life for patients.

What’s on the horizon for NF1-PN care?

The ReNeu trial is just the beginning. Ongoing studies are exploring how to refine treatment, predict malignant transformation, and personalize care. Trials like KOMET (selumetinib in adults)¹² and NF108-BINI (binimetinib in children and adults)¹³ are expanding our understanding of MEK inhibitors, while other observational studies^14-17 are helping identify high-risk patients earlier.

This growing research effort is reshaping the future of NF1 care. The INSPIRE-NF1 trial (NCT06541847) is evaluating HLX-1502, a novel targeted therapy, as part of a broader shift toward earlier, more proactive treatment.¹⁷ At the same time, the long-running natural history study (NCT00924196) continues to deepen our understanding of how NF1 progresses over time, highlighting variability in patient experiences and unmet needs.¹⁶

Efforts to predict malignant transformation are also gaining momentum. A prospective biomarker study (NCT05677594) is also underway, exploring how imaging, clinical, and genetic data might help predict malignant transformation – potentially enabling earlier, more targeted intervention.¹⁴ Biospecimen repositories and genomic profiling are playing a key role in these efforts.¹⁵ For example, the Johns Hopkins NF1 Biospecimen Repository is supporting translational research by collecting tumor and blood samples to advance genomic discovery.¹⁵

Check back here for more expert insights in the coming weeks, including interviews with leading clinicians.

References

1. Chong, 2025. Lifelong management of neurofibromatosis 1 patients. https://www.doi.org/10.3340/jkns.2025.0057
2. Fisher, 2022. Management of neurofibromatosis type 1-associated plexiform neurofibromas. https://www.doi.org/10.1093/neuonc/noac146
3. NORD, 2025. Neurofibromatosis 1. https://rarediseases.org/rare-diseases/neurofibromatosis-type-1-nf1/
4. Orphanet. Neurofibromatosis type 1. https://www.orpha.net/en/disease/detail/636
5. Copley-Merriman, 2021. Natural history and disease burden of neurofibromatosis type 1 with plexiform neurofibromas: A systematic literature review. https://www.doi.org/10.2147/ahmt.S303456
6. Imataka, 2025. Neurofibromatosis type 1 and MEK inhibition: A comprehensive review with focus on selumetinib therapy. https://www.doi.org/10.3390/jcm14145071
7. FDA, 2025. FDA approves selumetinib for pediatric patients 1 year of age and older with neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-pediatric-patients-1-year-age-and-older-neurofibromatosis-type-1
8. FDA, 2020. FDA approves selumetinib for neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-neurofibromatosis-type-1-symptomatic-inoperable-plexiform-neurofibromas
9. FDA, 2025. Highlights of prescribing information. Koselugo^®. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/213756Orig1s005lbl.pdf
10. FDA, 2025. Highlights of prescribing information. Jascayd^®. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218764s000lbl.pdf
11. FDA, 2025. FDA approves mirdametinib for adult and pediatric patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas not amenable to complete resection. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirdametinib-adult-and-pediatric-patients-neurofibromatosis-type-1-who-have-symptomatic
12. ClinicalTrials.gov, 2025. Efficacy and safety of selumetinib in adults with NF1 who have symptomatic, inoperable plexiform neurofibromas (KOMET). https://clinicaltrials.gov/study/NCT04924608
13. ClinicalTrials.gov, 2025. Phase II study of binimetinib in children and adults with NF1 plexiform neurofibromas (NF108-BINI). https://clinicaltrials.gov/study/NCT03231306
14. ClinicalTrials.gov, 2025. Multi-parametric biomarker development to predict malignant conversion in patients with neurofibromatosis type 1. https://www.clinicaltrials.gov/study/NCT05677594
15. Medicine, 2025. The Johns Hopkins NF1 biospecimen repository. https://www.hopkinsmedicine.org/kimmel-cancer-center/cancers-we-treat/pediatric/research-and-clinical-trials/pratilas/nf1-biospecimen-repository
16. ClinicalTrials.gov, 2025. Natural history study of patients with neurofibromatosis type I. https://clinicaltrials.gov/study/NCT00924196
17. ClinicalTrials.gov, 2025. A phase 2, open-label study to evaluate the safety and effects of HLX-1502 in patients with neurofibromatosis type 1 (INSPIRE-NF1). https://clinicaltrials.gov/study/NCT06541847?cond=hlx-1502&rank=1