Management of Adverse Events Associated With Selumetinib for Pediatric Patients With Neurofibromatosis Type 1 With Plexiform Neurofibromas

A panel of experts came to a consensus-level agreement on the prevention and management of certain adverse events potentially associated with selumetinib, an oral MEK1/2 inhibitor is the first treatment approved for pediatric patients with neurofibromatosis type 1 and plexiform neurofibromas (NF1-PN). While the safety profile of selumetinib is manageable, “evidence for the management of selumetinib-associated adverse events is mostly limited to clinical trials and expanded-access programs,” wrote Amedeo A Azizi, MD, Medical University of Vienna, Austria, and coauthors.

This expert panel consisted of 2 pediatric neuro-oncologists, 1 pediatric oncologist, 1 pediatrician, 1 neuropediatrician, 1 oncologist, 1 neurologist, 2 psychologists, and 1 dermatologist. All had clinical experience prescribing selumetinib and/or managing patients with NF1-PN. Using a literature review of current management recommendations and regulatory reports, a series of statements on adverse events with selumetinib was presented to the panel. The panel than edited or amended the statements and rated the extent to which they agreed with them. This resulted in a consensus-level agreement on 36 statements related to the prevention, early detection, and management of adverse events potentially associated with selumetinib.

The panel first reached a consensus on the relative observed frequency of potential adverse events associated with selumetinib, prioritizing each adverse event by the patient impact (including whether it required a treatment discontinuation) and frequency. The adverse events prioritized were: paronychia, acneiform rash, eczematous rash, psychological burden of adverse events, fatigue, creatine phosphokinase (CPK) elevation, retinal pigment epithelial detachment (RPED), weight gaine, central serous retinopathy (CSR), left ventricular ejection fraction (LVEF) reduction, hair loss, stomatitis, nausea and vomiting, peripheral edema, and diarrhea.

The panel noted that paronychia was among the most challenging of adverse events, while also being ranked high on both the frequency and impact on patients. It was agreed that this particular adverse event, as study authors wrote, “should be managed aggressively and be a key focus for healthcare practitioners.” Stomatitis was also highlighted, as “it can be associated with considerable pain and have great impact on a patient’s daily life.”

In conclusion, Dr Azizi et al, wrote that when a pediatric patient is initiated on selumetinib “various preventative measures and monitoring for early signs of toxicity should be taken” and highlighted the importance of patients and caregivers being “informed about potential [adverse events] and…aware of the various prevention and management strategies.” Overall, the report from this panel provides “a strong level of consensus from a multidisciplinary group to support previous recommendations regarding several aspects of the prevention and management of [adverse events] potentially associated with selumetinib.”

Source:

Azizi AA, Hargrace D, Passos J, et al. Consensus recommendations on management of selumetinib-associated adverse events in pediatric patients with neurofibromatosis type 1 and plexiform neurofibromas. Neurooncol Pract. 2024;11(5):515-531. doi:10.1093/nop/npae038