Selumetinib in Children with Inoperable Plexiform Neurofibromas.
N Engl J Med
; 382(15): 1430-1442, 2020 04 09.
Article
em En
| MEDLINE
| ID: mdl-32187457
ABSTRACT
BACKGROUND:
No approved therapies exist for inoperable plexiform neurofibromas in patients with neurofibromatosis type 1.METHODS:
We conducted an open-label, phase 2 trial of selumetinib to determine the objective response rate among patients with plexiform neurofibromas and to assess clinical benefit. Children with neurofibromatosis type 1 and symptomatic inoperable plexiform neurofibromas received oral selumetinib twice daily at a dose of 25 mg per square meter of body-surface area on a continuous dosing schedule (28-day cycles). Volumetric magnetic resonance imaging and clinical outcome assessments (pain, quality of life, disfigurement, and function) were performed at least every four cycles. Children rated tumor pain intensity on a scale from 0 (no pain) to 10 (worst pain imaginable).RESULTS:
A total of 50 children (median age, 10.2 years; range, 3.5 to 17.4) were enrolled from August 2015 through August 2016. The most frequent neurofibroma-related symptoms were disfigurement (44 patients), motor dysfunction (33), and pain (26). A total of 35 patients (70%) had a confirmed partial response as of March 29, 2019, and 28 of these patients had a durable response (lasting ≥1 year). After 1 year of treatment, the mean decrease in child-reported tumor pain-intensity scores was 2 points, considered a clinically meaningful improvement. In addition, clinically meaningful improvements were seen in child-reported and parent-reported interference of pain in daily functioning (38% and 50%, respectively) and overall health-related quality of life (48% and 58%, respectively) as well as in functional outcomes of strength (56% of patients) and range of motion (38% of patients). Five patients discontinued treatment because of toxic effects possibly related to selumetinib, and 6 patients had disease progression. The most frequent toxic effects were nausea, vomiting, or diarrhea; an asymptomatic increase in the creatine phosphokinase level; acneiform rash; and paronychia.CONCLUSIONS:
In this phase 2 trial, most children with neurofibromatosis type 1 and inoperable plexiform neurofibromas had durable tumor shrinkage and clinical benefit from selumetinib. (Funded by the Intramural Research Program of the National Institutes of Health and others; ClinicalTrials.gov number, NCT01362803.).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzimidazóis
/
Neurofibromatose 1
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Neurofibroma Plexiforme
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Quinases de Proteína Quinase Ativadas por Mitógeno
/
Inibidores de Proteínas Quinases
Tipo de estudo:
Etiology_studies
Limite:
Adolescent
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Child
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Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
N Engl J Med
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Namíbia