Selumetinib in children with neurofibromatosis type 1 and asymptomatic inoperable plexiform neurofibroma at risk for developing tumor-related morbidity. Issue 11 (25th April 2022)

• Record Type: Journal Article
• Authors: Gross, Andrea M; Glassberg, Brittany; Wolters, Pamela L; Dombi, Eva; Baldwin, Andrea; Fisher, Michael J; Kim, AeRang; Bornhorst, Miriam; Weiss, Brian D; Blakeley, Jaishri O; Whitcomb, Patricia; Paul, Scott M; Steinberg, Seth M; Venzon, David J; Martin, Staci; Carbonell, Amanda; Heisey, Kara; Therrien, Janet; Kapustina, Oxana; Dufek, Anne; Derdak, Joanne; Smith, Malcolm A; Widemann, Brigitte C
• Is Part Of: Neuro-oncology. Volume 24:Issue 11(2022)
• Page Start: 1978
• Page End: 1988
• Publication Date: 2022-04-25
• Subjects: MEK inhibitor -- neurofibromatosis type 1 -- patient-reported outcome measures -- plexiform neurofibroma -- selumetinib; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noac109
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Background: Selumetinib was recently approved for the treatment of inoperable symptomatic plexiform neurofibromas (PNs) in children with neurofibromatosis type 1 (NF1). This parallel phase II study determined the response rate to selumetinib in children with NF1 PN without clinically significant morbidity. Methods: Children with NF1 and inoperable PNs, which were not yet causing clinically significant morbidity but had the potential to cause symptoms, received selumetinib at 25 mg/m 2 orally twice daily (1 cycle = 28 days). Volumetric magnetic resonance imaging analysis and outcome assessments, including patient-reported (PRO), observer-reported, and functional outcome measures were performed every 4 cycles for 2 years, with changes assessed over time. A confirmed partial response (cPR) was defined as PN volume decrease of ≥20% on at least 2 consecutive scans ≥3 months apart. Results: 72% of subjects experienced a cPR on selumetinib. Participants received selumetinib for a median of 41 cycles (min 2, max 67) at data cutoff. Approximately half of the children rated having some target tumor pain at baseline, which significantly decreased by pre-cycle 13. Most objectively measured baseline functions, including visual, motor, bowel/bladder, or airway function were within normal limits and did not clinically or statistically worsen during treatment. Conclusions: Selumetinib resulted in PN shrinkage in most subjects with NF1 PN without clinically significant morbidity. No new PN-related symptoms developed while on selumetinib, and PRO measures indicated declines in tumor-related pain intensity. This supports that selumetinib treatment may prevent the development of PN-related morbidities, though future prospective studies are needed to confirm these results. Clinical Trial registration: ClinicalTrials.gov NCT01362803.