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@ARTICLE{Bouffet:283124,
      author       = {E. Bouffet and J. R. Hansford and M. L. Garrè and J. Hara
                      and A. Plant-Fox and I. Aerts and F. Locatelli and J. van
                      der Lugt and L. Papusha and F. Sahm$^*$ and U. Tabori and K.
                      J. Cohen and R. J. Packer and O. Witt$^*$ and L. Sandalic
                      and A. Bento Pereira da Silva and M. Russo and D. R.
                      Hargrave},
      title        = {{D}abrafenib plus {T}rametinib in {P}ediatric {G}lioma with
                      {BRAF} {V}600 {M}utations.},
      journal      = {The New England journal of medicine},
      volume       = {389},
      number       = {12},
      issn         = {0028-4793},
      address      = {Waltham, Mass.},
      publisher    = {MMS},
      reportid     = {DKFZ-2023-01911},
      pages        = {1108 - 1120},
      year         = {2023},
      abstract     = {Detection of the BRAF V600E mutation in pediatric low-grade
                      glioma has been associated with a lower response to standard
                      chemotherapy. In previous trials, dabrafenib (both as
                      monotherapy and in combination with trametinib) has shown
                      efficacy in recurrent pediatric low-grade glioma with BRAF
                      V600 mutations, findings that warrant further evaluation of
                      this combination as first-line therapy.In this phase 2
                      trial, patients with pediatric low-grade glioma with BRAF
                      V600 mutations who were scheduled to receive first-line
                      therapy were randomly assigned in a 2:1 ratio to receive
                      dabrafenib plus trametinib or standard chemotherapy
                      (carboplatin plus vincristine). The primary outcome was the
                      independently assessed overall response (complete or partial
                      response) according to the Response Assessment in
                      Neuro-Oncology criteria. Also assessed were the clinical
                      benefit (complete or partial response or stable disease for
                      ≥24 weeks) and progression-free survival.A total of 110
                      patients underwent randomization (73 to receive dabrafenib
                      plus trametinib and 37 to receive standard chemotherapy). At
                      a median follow-up of 18.9 months, an overall response
                      occurred in $47\%$ of the patients treated with dabrafenib
                      plus trametinib and in $11\%$ of those treated with
                      chemotherapy (risk ratio, 4.31; $95\%$ confidence interval
                      [CI], 1.7 to 11.2; P<0.001). Clinical benefit was observed
                      in $86\%$ of the patients receiving dabrafenib plus
                      trametinib and in $46\%$ receiving chemotherapy (risk ratio,
                      1.88; $95\%$ CI, 1.3 to 2.7). The median progression-free
                      survival was significantly longer with dabrafenib plus
                      trametinib than with chemotherapy (20.1 months vs. 7.4
                      months; hazard ratio, 0.31; $95\%$ CI, 0.17 to 0.55;
                      P<0.001). Grade 3 or higher adverse events occurred in
                      $47\%$ of the patients receiving dabrafenib plus trametinib
                      and in $94\%$ of those receiving chemotherapy.Among
                      pediatric patients with low-grade glioma with BRAF V600
                      mutations, dabrafenib plus trametinib resulted in
                      significantly more responses, longer progression-free
                      survival, and a better safety profile than standard
                      chemotherapy as first-line therapy. (Funded by Novartis;
                      ClinicalTrials.gov number, NCT02684058.).},
      keywords     = {Humans / Child / Proto-Oncogene Proteins B-raf: genetics /
                      Glioma: drug therapy / Glioma: genetics / Mutation /
                      dabrafenib (NLM Chemicals) / trametinib (NLM Chemicals) /
                      Proto-Oncogene Proteins B-raf (NLM Chemicals) / BRAF
                      protein, human (NLM Chemicals)},
      cin          = {B300 / B310 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B300-20160331 / I:(DE-He78)B310-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37733309},
      doi          = {10.1056/NEJMoa2303815},
      url          = {https://inrepo02.dkfz.de/record/283124},
}