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Multicenter Study
. 2025 Dec;175(3):1027-1037.
doi: 10.1007/s11060-025-05197-5. Epub 2025 Aug 13.

Real-world experience with selumetinib in children with neurofibromatosis type 1: a multicentric retrospective study

Claudia Santoro  1 , Mariachiara Servedio  2 , Maria Cristina Diana  3 , Irene Russo  4 , Elena Arkhangelskaya  5 , Gianluca Piccolo  6   7 , Andrea Santangelo  3   7 , Angela Mastronuzzi  8 , Antonella Cacchione  8 , May El Hachem  9 , Carmela Russo  10 , Mario Cirillo  11 , Ilaria Cecconi  12 , Antonio Grasso  13 , Mariateresa Loiotine  2 , Nicola Santoro  2 , Mariachiara Resta  14 , Carmela De Meco  15 , Consolata Soddu  16 , Eugenia Spreafico  17 , Bartolomeo Rossi  18 , Chiara Fossati  19 , Chiara Leoni  20 , Silverio Perrotta  4 , Teresa Perillo  2
Affiliations
Multicenter Study

Real-world experience with selumetinib in children with neurofibromatosis type 1: a multicentric retrospective study

Claudia Santoro et al. J Neurooncol. 2025 Dec.

Abstract

Purpose: Selumetinib is a MEK inhibitor indicated for pediatric patients with neurofibromatosis type 1 (NF1) and symptomatic inoperable plexiform neurofibromas (PNs).

Methods: This retrospective study collected data from 70 patients (aged 3 - 18 years) with NF1 and symptomatic inoperable PNs treated with selumetinib as part of compassionate use at 11 Italian centers between October 2018 and October 2024. Assessments included the clinical benefit rate (CBR) after 24 months and at the last observation. Major response (MR) was defined as a ≥ 50% reduction from baseline in tumor volume. Adverse events (AEs), patient-reported pain and quality of life (QoL), and Eastern Cooperative Oncology Group performance status (ECOG PS), were also evaluated.

Results: Of 45/70 patients with available natural history data at C0, 33/45 (73.3%) had progressive disease (PD). Radiological evaluation at C6 in 17/33 patients showed 16 (94.1%) had stable disease (SD) or partial response (PR). 52/58 patients (91.5%) had SD or PR/MR at C12; final response at last radiological follow-up was PD (7.7%), SD (42.3%), PR (30.8%) and MR (19.2%). CBR was 83.3% (24/70) at C24 and 91.5% (43/47) at last radiological follow-up. Selumetinib significantly reduced pain perception and improved QoL and ECOG PS. The type of response at C6 seems to predict response at C12 and at last observation. Adverse events were generally mild (78% grade ≤ 2).

Conclusion: Our findings suggest that the response after 6 and 12 selumetinib cycles may predict long-term outcomes, providing clinicians with an early indicator for therapeutic decision-making.

Trial registration number: Not applicable.

Keywords: Clinical benefit rate; Neurofibromatosis type 1; Plexiform neurofibroma; Quality of life; Safety; Selumetinib.

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Conflict of interest statement

Declarations. Competing interests: C.S. received payment for scientific consultation and speaker honoraria from Alexion, AstraZeneca Rare Disease; participated on a data safety monitoring/advisory board for Alexion, AstraZeneca Rare Disease; received payment for scientific consultation from IQVIA and Atheneum; and held a leadership or fiduciary role for ANF patient advocacy. T.P. received payment for scientific consultation and speaker honoraria from Alexion, AstraZeneca Rare Disease; and participated on an advisory board for Alexion, AstraZeneca Rare Disease. A.M. received speaker honoraria from Alexion, AstraZeneca Rare Disease and participated on an advisory board for Ipsen. C.L. participated in the SeluPASS steering committee. All the other authors declare no conflict of interest. Ethics approval: This study was approved by the territorial Ethics Committee of the Polyclinic of Bari, Italy, on April 24, 2024, and conducted in accordance with the Helsinki Declaration, Good Clinical Practice guidelines, and all applicable laws and regulations. Consent to participate: Written informed consent to participate was obtained from patients aged 18 years, and from parents/legal guardians of patients aged < 18 years. Consent to publish: Not applicable.

Figures

Fig. 1
Fig. 1
Graphical representation of symptoms and signs of plexiform neurofibromas with their frequency and anatomical location of causative plexiform neurofibromas
See this image and copyright information in PMC

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