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@ARTICLE{Menzer:147211,
      author       = {C. Menzer and A. M. Menzies and M. S. Carlino and I.
                      Reijers and E. J. Groen and T. Eigentler and J. W. B. de
                      Groot and A. A. M. van der Veldt and D. B. Johnson and F.
                      Meiss and M. Schlaak and B. Schilling and H. M. Westgeest
                      and R. Gutzmer and C. Pföhler and F. Meier and L. Zimmer
                      and K. P. M. Suijkerbuijk and T. Haalck and K.-M. Thoms and
                      K. Herbschleb and J. Leichsenring and A. Menzer and A.
                      Kopp-Schneider$^*$ and G. V. Long and R. Kefford and A. Enk
                      and C. U. Blank and J. C. Hassel},
      title        = {{T}argeted {T}herapy in {A}dvanced {M}elanoma {W}ith {R}are
                      {BRAF} {M}utations.},
      journal      = {Journal of clinical oncology},
      volume       = {37},
      number       = {33},
      issn         = {1527-7755},
      address      = {Alexandria, Va.},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2019-02337},
      pages        = {3142-3151},
      year         = {2019},
      note         = {37(33):3142-3151},
      abstract     = {BRAF/MEK inhibition is a standard of care for patients with
                      BRAF V600E/K-mutated metastatic melanoma. For patients with
                      less frequent BRAF mutations, however, efficacy data are
                      limited.In the current study, 103 patients with metastatic
                      melanoma with rare, activating non-V600E/K BRAF mutations
                      that were treated with either a BRAF inhibitor (BRAFi), MEK
                      inhibitor (MEKi), or the combination were included. BRAF
                      mutation, patient and disease characteristics, response, and
                      survival data were analyzed.Fifty-eight patient tumors
                      $(56\%)$ harbored a non-E/K V600 mutation, 38 $(37\%)$ a
                      non-V600 mutation, and seven had both V600E and a rare BRAF
                      mutation $(7\%).$ The most frequent mutations were V600R
                      $(43\%;$ 44 of 103), L597P/Q/R/S $(15\%;$ 15 of 103), and
                      K601E $(11\%;$ 11 of 103). Most patients had stage IV
                      disease and $42\%$ had elevated lactate dehydrogenase at
                      BRAFi/MEKi initiation. Most patients received combined
                      BRAFi/MEKi $(58\%)$ or BRAFi monotherapy $(37\%).$ Of the 58
                      patients with V600 mutations, overall response rate to BRAFi
                      monotherapy and combination BRAFi/MEKi was $27\%$ (six of
                      22) and $56\%$ (20 of 36), respectively, whereas median
                      progression-free survival (PFS) was 3.7 months and 8.0
                      months, respectively (P = .002). Of the 38 patients with
                      non-V600 mutations, overall response rate was $0\%$ (zero of
                      15) to BRAFi, $40\%$ (two of five) to MEKi, and $28\%$ (five
                      of 18) to combination treatment, with a median PFS of 1.8
                      months versus 3.7 months versus 3.3 months, respectively.
                      Multivariable analyses revealed superior survival (PFS and
                      overall survival) with combination over monotherapy in rare
                      V600 and non-V600 mutated melanoma.Patients with rare BRAF
                      mutations can respond to targeted therapy, however, efficacy
                      seems to be lower compared with V600E mutated melanoma.
                      Combination BRAFi/MEKi seems to be the best regimen for both
                      V600 and non-V600 mutations. Yet interpretation should be
                      done with care because of the heterogeneity of patients with
                      small sample sizes for some of the reported mutations.},
      cin          = {C060},
      ddc          = {610},
      cid          = {I:(DE-He78)C060-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31580757},
      doi          = {10.1200/JCO.19.00489},
      url          = {https://inrepo02.dkfz.de/record/147211},
}