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. 2025 May 17;7(1):vdaf101.
doi: 10.1093/noajnl/vdaf101. eCollection 2025 Jan-Dec.

Selumetinib in pediatric patients with neurofibromatosis type 1 and plexiform neurofibroma: Propensity score analysis of SPRINT vs. natural history control arm

Ayo Adeyemi  1 , Andrea M Gross  2 , Andrea Baldwin  3 , Eva Dombi  2 , Brigitte C Widemann  2 , Kyaw Joe Sint  1
Affiliations

Selumetinib in pediatric patients with neurofibromatosis type 1 and plexiform neurofibroma: Propensity score analysis of SPRINT vs. natural history control arm

Ayo Adeyemi et al. Neurooncol Adv. .

Abstract

Background: Selumetinib is approved in children aged ≥ 2 years (USA) with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN) based on data from SPRINT (NCT01362803). This analysis estimated PN progression risk with selumetinib in SPRINT versus age-matched patients from the National Cancer Institute NF1 Natural History (NH) study (NCT00924196), accounting for differences in baseline characteristics using propensity score (PS) methods.

Methods: Differences in baseline characteristics between the cohorts were assessed. PSs based on age, sex, race, weight, height, and PN (location, volume, and progression status) were used in 1:1 PS matching without replacement, stabilized inverse probability of treatment weighting (sIPTW), and 1:2 PS matching with replacement as sensitivity analyses. The effect of selumetinib (maximum follow-up 5.6 years) on progression risk was evaluated using univariate and multivariable Cox models (adjusted for baseline characteristics) of progression-free survival.

Results: Before PS matching, patient baseline characteristics (n = 50 SPRINT; n = 75 NH) were generally balanced (standardized difference ≤ 0.2), except PN location (0.51) and PN status (0.60). Following 1:1 PS matching (n = 37), all characteristics were balanced except PN status (standardized difference 0.25). Balance was achieved with sIPTW and 1:2 PS matching (n = 46:43). Progression-free survival hazard ratios (95% confidence interval) were 0.11 (0.05-0.25), 0.11 (0.04-0.29), 0.12 (0.06-0.25), and 0.11 (0.06-0.24) (all P < .001) for direct comparison, 1:1 PS matching, sIPTW, and 1:2 PS matching, respectively.

Conclusions: Reduction in risk of NF1-related PN progression with selumetinib was consistent with direct comparison and statistically significant, robust, and comparable across PS methods.

Trial registration: ClinicalTrials.gov, NCT01362803. Registered May 27, 2011, https://clinicaltrials.gov/study/NCT01362803.

Keywords: effect of treatment; neurofibromatosis type 1; plexiform neurofibromas; propensity score analysis; selumetinib.

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Conflict of interest statement

A.A. reports employment, and owns stocks with, Alexion, AstraZeneca Rare Disease. A.M.G., A.B., and B.C.W. declare no conflicts of interest. A.B.E.D. served as an unpaid volunteer for Response Evaluation in Neurofibromatosis and Schwannomatosis and Neurofibromatosis Clinical Trials Consortium. K.J.S. is an ex-employee of, and owns stocks with, Alexion, AstraZeneca Rare Disease.

Figures

Figure 1.
Figure 1.
Flowchart of patients eligible for propensity score analysis. Abbreviations: NF1-PN, neurofibromatosis type 1-related plexiform neurofibroma; NH, Natural History; PN, plexiform neurofibroma.
Figure 2.
Figure 2.
Kaplan–Meier curves for PFS before and after propensity score analysis. Abbreviations: HR, hazard ratio; IPTW, inverse probability of treatment weighting; NH, Natural History; PFS, progression-free survival.
See this image and copyright information in PMC

References

    1. Hirbe AC, Gutmann DH.. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol. 2014;13(8):834–843. - PubMed
    1. Bergqvist C, Servy A, Valeyrie-Allanore L, et al. ; NF France Network. Neurofibromatosis 1 French national guidelines based on an extensive literature review since 1966. Orphanet J Rare Dis. 2020;15(1):37. - PMC - PubMed
    1. Baldo F, Magnolato A, Barbi E, Bruno I.. Selumetinib side effects in children treated for plexiform neurofibromas: first case reports of peripheral edema and hair color change. BMC Pediatr. 2021;21(1):67. - PMC - PubMed
    1. Ferner RE. Neurofibromatosis 1. Eur J Hum Genet. 2007;15(2):131–138. - PubMed
    1. Gross AM, Singh G, Akshintala S, et al. Association of plexiform neurofibroma volume changes and development of clinical morbidities in neurofibromatosis 1. Neuro Oncol. 2018;20(12):1643–1651. - PMC - PubMed

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