Response to trametinib treatment in progressive pediatric low-grade glioma patients.
BRAF
MAPK pathway
MEK inhibitor
NF1
Pediatric low-grade glioma
Targeted therapy
Trametinib
Journal
Journal of neuro-oncology
ISSN: 1573-7373
Titre abrégé: J Neurooncol
Pays: United States
ID NLM: 8309335
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
02
08
2020
accepted:
29
09
2020
pubmed:
8
10
2020
medline:
20
8
2021
entrez:
7
10
2020
Statut:
ppublish
Résumé
A hallmark of pediatric low-grade glioma (pLGG) is aberrant signaling of the mitogen activated protein kinase (MAPK) pathway. Hence, inhibition of MAPK signaling using small molecule inhibitors such as MEK inhibitors (MEKi) may be a promising strategy. In this multi-center retrospective centrally reviewed study, we analyzed 18 patients treated with the MEKi trametinib for progressive pLGG as an individual treatment decision between 2015 and 2019. We have investigated radiological response as per central radiology review, molecular classification and investigator observed toxicity. We observed 6 partial responses (PR), 2 minor responses (MR), and 10 stable diseases (SD) as best overall responses. Disease control rate (DCR) was 100% under therapy. Responses were observed in KIAA1549:BRAF- as well as neurofibromatosis type 1 (NF1)-driven tumors. Median treatment time was 12.5 months (range: 2 to 27 months). Progressive disease was observed in three patients after cessation of trametinib treatment within a median time of 3 (2-4) months. Therapy related adverse events occurred in 16/18 patients (89%). Eight of 18 patients (44%) experienced severe adverse events (CTCAE III and/or IV; most commonly skin rash and paronychia) requiring dose reduction in 6/18 patients (33%), and discontinuation of treatment in 2/18 patients (11%). Trametinib was an active and feasible treatment for progressive pLGG leading to disease control in all patients. However, treatment related toxicity interfered with treatment in individual patients, and disease control after MEKi withdrawal was not sustained in a fraction of patients. Our data support in-class efficacy of MEKi in pLGGs and necessity for upfront randomized testing of trametinib against current standard chemotherapy regimens.
Identifiants
pubmed: 33026636
doi: 10.1007/s11060-020-03640-3
pii: 10.1007/s11060-020-03640-3
pmc: PMC7609413
doi:
Substances chimiques
Antineoplastic Agents
0
Pyridones
0
Pyrimidinones
0
trametinib
33E86K87QN
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
499-510Subventions
Organisme : Brain Tumour Charity
ID : GN-000382
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