Impact of selumetinib on pain in adults with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas: An in-depth analysis from KOMET
Year: 2026
Type: article
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 the impact of selumetinib (ARRY-142886, AZD6244) 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 measures included chronic and spike target PN pain intensity (PAin INtensity Scale for Plexiform Neurofibromas [PAINS-pNF]; daily); pain interference with daily activities (Pain Interference Index for Plexiform Neurofibromas [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 a 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.
Source: Neuro-Oncology Practice
DOI: 10.1093/nop/npag083
Authors: Said Farschtschi, Carolina Barnett-Tapia, Alice Chen, Angela Mastronuzzi, Juan Manuel Sepúlveda-Sánchez, Yi-Cheng Zhu, Gail Doughton, Ayo Adeyemi, Rosa Lamarca, Josephine Norquist, Pamela L Wolters, KOMET study investigators, Alexander Lee, Angela Swampillai, Beniamin Bokhyan, Brian Van Tine, Cordula Matthies, Eva Dombi, Geraldine O’Sullivan Coyne, Hans Shuhaiber, Ignacio Blanco, James R Whittle, Jan Styczynski, Laura Fertitta, Luiz Guilherme Darrigo, Maëlla Severino-Freire, Maria D D’Agostino, Marina Dorofeeva, Marica Eoli, Martin Schuhmann, Pierre Wolkenstein, Pinan Liu, Robert Nakayama, Rodrigo Perez Pereira, Silverio Perrotta, Staci Martin, Viviane Sonaglio, Xinghua Gao, Yemima Berman, Yoshihiro Nishida, Yoshimasa Nobeyama, Zhongping Chen
Institutions: University Medical Center Hamburg-Eppendorf, University Health Network, University of Toronto, National Cancer Institute, Università Cattolica del Sacro Cuore, Bambino Gesù Children's Hospital, Hospital Universitario 12 De Octubre, Chinese Academy of Medical Sciences & Peking Union Medical College, Peking Union Medical College Hospital, AstraZeneca (United Kingdom), Alexion Pharmaceuticals (United States), Merck & Co., Inc., Rahway, NJ, USA (United States), National Institutes of Health, Center for Cancer Research
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,036
Funder: AstraZeneca
OpenAlex ID: W7203663502
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