ESMO 2026: Update on NF1‑PN management
By Laura Boyd
People with neurofibromatosis type 1 (NF1)-associated symptomatic plexiform neurofibromas (PN) may achieve sustained tumor volume reduction with longer‑term MEK inhibition, while surgical management continues to carry risks and likelihood of recurrence, according to data presented at the ESMO Sarcoma and Rare Cancers Congress 2026.
Presenting long‑term follow‑up data from the phase 2b ReNeu trial, Angela C. Hirbe (Washington University School of Medicine, St Louis, Missouri, USA) reported that MEK inhibition with mirdametinib demonstrated durable responses in adults and children with inoperable NF1‑PN. Mirdametinib is approved in the USA and Europe for patients aged ≥2 years.
At the data cutoff, 58 adults and 56 children received mirdametinib for a median treatment duration of 21.8 and 25.4 months, respectively. Among patients eligible for optional long‑term follow‑up, more than 80% in each age group continued therapy. Across the treatment and follow‑up phases combined, blinded independent central review confirmed an overall response rate (ORR) of 47% in adults and 55% in children.
Most responders in both cohorts achieved deep responses, defined as a reduction in target PN volume of >50% from baseline. Median best percentage change reached was –41% in adults and –43% in children. Duration of response was not reached at the time of analysis, suggesting sustained tumor control with prolonged treatment.
Mirdametinib maintained a manageable safety profile, with no new safety signals reported. Common treatment-related adverse events included dermatitis acneiform, diarrhea, nausea, and vomiting in adults, and diarrhea, dermatitis acneiform, and paronychia in children. Grade ≥3 adverse events occurred in 17% of adults and 25% of pediatric patients. Hirbe concluded that “longer duration of mirdametinib demonstrated improved confirmed ORR, [and] additional deep responses in adults and children.”
Complementary data highlighted the challenges of surgical management. Anastasia Tararykova (National Medical Research Center of Oncology, Moscow, Russian Federation) reported outcomes following complex surgical resection of symptomatic PN in adults with NF1. In a retrospective analysis of 15 patients, surgery was associated with a median intraoperative blood loss of 700 mL and wound‑healing complications in 28% of patients. Disease recurrence occurred in 42% of cases, and there was one perioperative death caused by coagulopathy following massive blood loss.
Larger PN volume correlated with longer operative time, increased blood loss, wound complications, and tumor regrowth. A small number of patients initiated postoperative MEK inhibitor therapy with selumetinib, reflecting what Tararykova described as “a trend toward combined management, in which aggressive surgery may be justified when followed by timely initiation of a MEK inhibitor… [that] may help prevent PN regrowth and improve or maintain long-term clinical and radiologic outcomes.”
Together, these findings highlight an evolving treatment landscape for NF1‑associated PN, in which the risks and limited durability of surgery contrast with the potential sustained disease control observed with MEK inhibition.
Review more expert insights on NF1 from EANO 2025.
Developed by EPG Health for Medthority, independently of any sponsor.
