Selumetinib Shows Efficacy, Safety Among Pediatric and Adult Patients With Neurofibromatosis Type 1 and Plexiform Neurofibroma

According to a phase 2 trial, the oral selective MEK inhibitor selumetinib decreased the plexiform neurofibroma (PN) volume among a majority of pediatric and adult patients with neurofibromatosis type 1 (NF1), while also showing efficacy in non-malignant diverse NF1 manifestations.

Recently in a phase 2 trial, selumetinib demonstrated efficacy in reducing PN in pediatric patients with NF1. However, the safety and efficacy of this treatment among adult patients with PN and its effectiveness in other NF1 manifestations such as neurocognitive function, growth reduction, etc, has not yet been shown.

In this single-arm, open-label, phase 2 trial, 59 pediatric and 30 adult patients with NF1 and inoperable, symptomatic, or potentially morbid, measurable PN of at least 3 cm were enrolled. Patients received 20 or 25 mg/m2 or 50 mg once every 12 hours for 2 years. The primary outcomes of this trial were safety and pharmacokinetics, while secondary outcomes included PN reduction, operability, pain, quality of life, and neurocognitive functions.

Of the 90 patients in the intention-to-treat population, 88 showed a median reduction of 40.8% for PN volume. There was 1 pediatric patient who did not show any change in volume. Of 89 patients included in the per-protocol analysis, the response rate was 98.9%, with 81% showing a partial response. All patients who received 26 cycles of selumetinib (n = 42) achieved a partial response. Scoring related to neurocognitive function, including verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ, significantly improved in both pediatric and adult patients. Among prepubertal patients, there were increases in height score and growth velocity (P < .05). There was a significant decrease of café-au-lait spot intensity (P < .05). For both pediatric and adult patients, there were improvements in quality of life and pain scores.

The most common adverse event was paronychia (n = 62), followed by aceniform rash, and skin infection. Of all adverse events, 4.7% were grade 2, and the rest were grade 1. Adverse event frequency was highest during cycle 1 and decreased as cycles progressed. Regardless of severity of the adverse event, all were resolved with supportive therapy and without drug discontinuation.

Study authors concluded this trial “showed encouraging results in reducing PN regardless of age. Importantly selumetinib demonstrated a wide range of beneficial effects on the systemic manifestations of NF1.” They added, “considering its significant effectiveness in both children and adults with NF1, continued and sustained treatment with selumetinib should be considered along with safety monitoring.”

Source:

Kim H, Yoo HM, Kim EK, et al. Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma. Neuro-Oncology. Published online: July 8, 2024. doi:10.1093/neuonc/noae121