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@ARTICLE{Selt:163930,
      author       = {F. Selt$^*$ and C. M. van Tilburg$^*$ and B. Bison and P.
                      Sievers$^*$ and I. Harting and J. Ecker$^*$ and K. W.
                      Pajtler$^*$ and F. Sahm$^*$ and A. Bahr and M. Simon and D.
                      T. W. Jones$^*$ and L. Well and V.-F. Mautner and D.
                      Capper$^*$ and P. Hernáiz Driever and A. Gnekow and S. M.
                      Pfister$^*$ and O. Witt$^*$ and T. Milde$^*$},
      title        = {{R}esponse to trametinib treatment in progressive pediatric
                      low-grade glioma patients.},
      journal      = {Journal of neuro-oncology},
      volume       = {149},
      number       = {3},
      issn         = {1573-7373},
      address      = {Dordrecht [u.a.]},
      publisher    = {Springer Science + Business Media B.V},
      reportid     = {DKFZ-2020-02154},
      pages        = {499-510},
      year         = {2020},
      note         = {#EA:B310#LA:B310# 2020 Sep;149(3):499-510},
      abstract     = {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.},
      cin          = {B310 / HD01 / B300 / B062 / B360 / BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)B310-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B300-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)B360-20160331 / I:(DE-He78)BE01-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33026636},
      doi          = {10.1007/s11060-020-03640-3},
      url          = {https://inrepo02.dkfz.de/record/163930},
}