Impact of selumetinib on pain in adults with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas: an in-depth analysis from KOMET

Abstract Background Pain is common in adults with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PN). Pain reduction and improved function are benefits documented along with PN volume shrinkage following medical treatment. This in-depth secondary and exploratory analysis from KOMET (NCT04924608) further evaluates selumetinib (ARRY-142886, AZD6244) impact on pain in adults with NF1-PN. Methods Participants were randomized to selumetinib (25 mg/m2 twice-daily) or placebo with crossover to selumetinib at end of Cycle 12 (open-label period) or earlier if confirmed radiological progression. Electronic patient-reported outcome (PRO) measures included chronic and spike target PN pain intensity (PAINS-pNF; daily); pain interference with daily activities (PII-pNF; site visits); pain medication use for chronic and spike target PN pain (e-Diary; daily); and patient global impression of severity/change for PN-related pain (PGIS/PGIC; site visits). Results At Cycle 12, selumetinib participants were ≥1.9 times more likely (odds ratio range: 1.9–2.7) to have clinically meaningful improvement in each pain-related endpoint (PAINS-pNF, PII-pNF) and decreased pain medication use from baseline versus placebo. Clinically meaningful improvement in ≥ 1 pain-related endpoint was reported by 62% and 42% of selumetinib and placebo participants, respectively. In the open-label period, there were rapid improvements in pain-related endpoints in placebo participants after crossover to selumetinib. Improvements observed in the selumetinib group during the randomized period in PAINS-pNF chronic and spike target PN pain intensity scores, PII-pNF, and proportion of participants with decrease in pain medication use were maintained over the open-label period. Conclusion Selumetinib improved PN-related pain and reduced PN volume in adults with NF1-PN.

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Journal
Neuro-Oncology Practice
Published
2026-08-17
DOI
https://doi.org/10.1093/nop/npag083
Primary Topic
Neurofibromatosis and Schwannoma Cases
Type
article
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article

Impact of selumetinib on pain in adults with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas: an in-depth analysis from KOMET

Viviane Sonaglio, James Richard Whittle, Silverio Perrotta, Yoshimasa Nobeyama et al.
Neuro-Oncology Practice
Neurofibromatosis and Schwannoma Cases
article

Impact of selumetinib on pain in adults with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas: an in-depth analysis from KOMET

Viviane Sonaglio, James Richard Whittle, Silverio Perrotta, Yoshimasa Nobeyama, Marica Eoli, Rosa Lamarca, Luiz Guilherme Darrigo, Ignacio Blanco, Cordula Matthies, Juan Manuel Sepúlveda-Sánchez, Laura Fertitta, Rodrigo Perez Pereira, Alice Chen, Ayo Adeyemi, Pierre Wolkenstein, Gail Doughton, Robert Nakayama, Marina Dorofeeva, Angela Mastronuzzi, Yemima Berman, Angela Swampillai, Xinghua Gao, Maëlla Severino-Freire, Martin Schuhmann, Hans Shuhaiber, Alexander Lee, Beniamin Bokhyan, Jan Styczynski, Said Farschtschi, Josephine Norquist, Staci Martin, Yi-Cheng Zhu, Geraldine O’Sullivan Coyne, Maria D'Agostino, Brian Van Tine, Eva Dombi, Pinan Liu, Zhongping Chen, Carolina Barnett-Tapia, Yoshihiro Nishida, the KOMET study investigators, Pamela L Wolters
article en

Abstract

Abstract Background Pain is common in adults with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PN). Pain reduction and improved function are benefits documented along with PN volume shrinkage following medical treatment. This in-depth secondary and exploratory analysis from KOMET (NCT04924608) further evaluates selumetinib (ARRY-142886, AZD6244) impact on pain in adults with NF1-PN. Methods Participants were randomized to selumetinib (25 mg/m2 twice-daily) or placebo with crossover to selumetinib at end of Cycle 12 (open-label period) or earlier if confirmed radiological progression. Electronic patient-reported outcome (PRO) measures included chronic and spike target PN pain intensity (PAINS-pNF; daily); pain interference with daily activities (PII-pNF; site visits); pain medication use for chronic and spike target PN pain (e-Diary; daily); and patient global impression of severity/change for PN-related pain (PGIS/PGIC; site visits). Results At Cycle 12, selumetinib participants were ≥1.9 times more likely (odds ratio range: 1.9–2.7) to have clinically meaningful improvement in each pain-related endpoint (PAINS-pNF, PII-pNF) and decreased pain medication use from baseline versus placebo. Clinically meaningful improvement in ≥ 1 pain-related endpoint was reported by 62% and 42% of selumetinib and placebo participants, respectively. In the open-label period, there were rapid improvements in pain-related endpoints in placebo participants after crossover to selumetinib. Improvements observed in the selumetinib group during the randomized period in PAINS-pNF chronic and spike target PN pain intensity scores, PII-pNF, and proportion of participants with decrease in pain medication use were maintained over the open-label period. Conclusion Selumetinib improved PN-related pain and reduced PN volume in adults with NF1-PN.

Neuro-Oncology Practice
Università Cattolica del Sacro Cuore (IT), Merck & Co., Inc., Rahway, NJ, USA (United States) (US), University Health Network (CA), Universität Hamburg (DE), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking Union Medical College Hospital (CN), Hospital Universitario 12 De Octubre (ES), University Medical Center Hamburg-Eppendorf (DE), AstraZeneca (Singapore) (SG), Bambino Gesù Children's Hospital (IT), Alexion Pharmaceuticals (United States) (US), AstraZeneca (Poland) (PL), United Therapeutics (United States) (US), National Cancer Institute (US), Alexion Pharma (Switzerland) (CH)
Good health and well-being
Openalex Percentile: Top 10%
Neurofibromatosis and Schwannoma Cases
DOIOpen Access PDFOpenAlex
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