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.