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@ARTICLE{Fangusaro:300575,
author = {J. Fangusaro and A. Onar-Thomas and T. Young Poussaint and
S. Lensing and A. H. Ligon and N. Lindeman and A. Banerjee
and L. B. Kilburn and A. Lenzen and N. Pillay-Smiley and I.
F. Pollack and N. J. Robison and S. Partap and I. Qaddoumi
and D. Landi and D. Jones$^*$ and C. F. Stewart and M.
Fouladi and I. J. Dunkel},
title = {{A} {P}hase 2 {PBTC} {S}tudy of {S}elumetinib for
{R}ecurrent/{P}rogressive {P}ediatric {L}ow-{G}rade
{G}lioma: {S}trata 2, 5, and 6 with {L}ong-term {O}utcomes
on {S}trata 1, 3, and 4.},
journal = {Neuro-Oncology},
volume = {nn},
issn = {1522-8517},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2025-00808},
pages = {nn},
year = {2025},
note = {epub},
abstract = {PBTC-029B was a phase 2 trial evaluating efficacy of
selumetinib in children with recurrent/progressive low-grade
glioma. We report results of strata 2, 5, and 6 with updated
survivals for strata 1, 3, and 4.Stratum 2 included
recurrent/progressive pilocytic astrocytoma (PA) not
associated with neurofibromatosis type-1 (NF1) that screened
negative for the BRAF-KIAA1549 fusion and BRAFV600E
mutation. Stratum 5 enrolled non-PA that screened positive
for one of the BRAF aberrations. Stratum 6 enrolled children
who consented to tissue screening, but there was an assay
failure. For long-term survivals, stratum 1 included non-NF1
PA positive for one of the BRAF aberrations; stratum 3
included NF1-associated pLGG; and stratum 4 included non-NF1
optic pathway/hypothalamic tumors.Stratum 2: among 14
evaluable patients, there was 1 partial response (PR), 7
stable disease (SD) and 6 progressive disease (PD); overall
response rate (ORR) was $7.1\%.$ Two-year progression-free
survival (PFS)/overall survival (OS) were $57.1\%/100\%,$
respectively. Stratum 5: among 23 evaluable patients, there
was 1 complete response (CR), 4 PR, 12 SD, and 6 PD; ORR was
$21.7\%.$ Two-year PFS/OS were $74.8\%/100\%,$ respectively.
Stratum 6: among 26 evaluable patients, there were 7 PR, 14
SD, and 5 PD; ORR was $26.9\%.$ Two-year PFS/OS were
$72.0\%/100\%,$ respectively. The median follow-up for
patients on strata 1, 3, and 4 without events are 60.4,
60.4, and 58.1 months, and 5-year PFS/OS were
$30.8\%/88.9\%,$ $54.2\%/100\%,$ and $51.0\%/100\%,$
respectively.Selumetinib provided stability and responses
across many pLGG subgroups, and some patients achieved
prolonged disease control without additional therapy.},
keywords = {Recurrent (Other) / and MEK inhibitor (Other) / pediatric
low-grade glioma (pLGG) (Other) / selumetinib (Other)},
cin = {B360},
ddc = {610},
cid = {I:(DE-He78)B360-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40241281},
doi = {10.1093/neuonc/noaf065},
url = {https://inrepo02.dkfz.de/record/300575},
}