Adult Patients' Experiences With Selumetinib Treatment Versus Placebo for Neurofibromatosis Type One-Plexiform Neurofibroma Associated Symptoms and Their Impacts: A Qualitative Sub-study of a Phase Three, Placebo-controlled Trial (KOMET)
Angela Swampillai1, Ignacio Blanco2, Carolina Barnett-Tapia3, Alexander Lee4, Angela Mastronuzzi5, Cordula Matthies6, Silverio Perrotta7, Marica Eoli8, Hans Shuhaiber9, Ayo Adeyemi10, Gail Doughton10, Randolph de la Rosa Rodriguez10, Said Farschtschi11
1Guy's and St Thomas' Hospital NHS Foundation Trust, 2Hospital Germans Trias i Pujol, 3University Health Network, University of Toronto, 4The Christie NHS Foundation Trust, 5IRCCS Bambino Gesù Children's Hospital, 6University Hospital Würzburg, 7University of Campania Luigi Vanvitelli, 8Fondazione IRCCS Besta, 9University of Florida Clinical Research Center, 10AstraZeneca Rare Disease, 11University Medical Center Hamburg-Eppendorf
Objective:
To enhance understanding of patient experiences with selumetinib (ARRY-142886, AZD6244; MEK1/2 inhibitor) treatment versus placebo in adults with NF1-PN in KOMET (NCT04924608).
Background:
KOMET evaluated efficacy and safety of selumetinib in adults with NF1 and symptomatic, inoperable PN. At study initiation, no approved therapies existed.
Design/Methods:
A qualitative interview sub-study was conducted with KOMET participants in Germany, UK, Italy, Spain, Canada and USA. Trained moderators conducted three 1:1 semi-structured interviews via teleconference (February 2022–December 2024). Participants were enrolled in KOMET and consented to the sub-study.
Results:
Sub-study participants were aged 18-59 years, 52% were women and 80% White. At interview 1 (baseline: N=25, n=13 selumetinib; n=12 placebo), main locations of target PNs were head/neck (n=7, 28%) and trunk (n=6, 24%). Most common symptoms were chronic pain (80%), sensitivity/numbness (48%), episodic/spike pain (36%), swelling (32%), and itching (28%). Highest reported impacts were on restricted body movements (56%), exercise (52%), and impact on school/work (44%). At interview 2 (cycle 12, N=22 [n=12 selumetinib; n=10 placebo]), all except one selumetinib participants reported improvements in symptom and impact burden with noticeable decreases in pain, tingling, PN size, and resulting improvement in sleep and fatigue and body movements, while placebo participants observed no notable changes. By interview 3 (~20 months post-randomization: N=16, n=8 selumetinib; n=8 crossover [12 cycles placebo + 8 cycles selumetinib]), the observed changes from interview 2 were sustained or further improved for most selumetinib participants. Crossover participants (~8 months on selumetinib post-crossover) reported similar benefits as the selumetinib group participants, including improved sleep, mobility, and a greater ability to engage in physical and social activities.
Conclusions:
This study provides insights into the experience of adults with NF1-PN during KOMET, and further demonstrates the positive effect of selumetinib on symptoms by adding to the objective parameters and patient-reported outcomes in the primary analysis publication.
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