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@ARTICLE{Stintzing:298573,
      author       = {S. Stintzing$^*$ and S. Klein-Scory and L. Fischer von
                      Weikersthal and M. Fuchs and F. Kaiser and K. Heinrich and
                      D. P. Modest and R.-D. Hofheinz and T. Decker and A. Gerger
                      and S. Angermeier and H. Rumpold and A. Dickhut and L.
                      Öhler and B. Gruenberger and D. Niedersuess-Beke and M.
                      Sandmann and T. Winder and J. Trojan and G. Prager and S.
                      Held and J. Kumbrink$^*$ and W. Schmiegel and A. Baraniskin
                      and V. Heinemann$^*$},
      title        = {{B}aseline {L}iquid {B}iopsy in {R}elation to
                      {T}issue-{B}ased {P}arameters in {M}etastatic {C}olorectal
                      {C}ancer: {R}esults {F}rom the {R}andomized {FIRE}-4
                      ({AIO}-{KRK}-0114) {S}tudy.},
      journal      = {Journal of clinical oncology},
      volume       = {43},
      number       = {12},
      issn         = {0732-183X},
      address      = {Alexandria, Va.},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2025-00290},
      pages        = {1463-1473},
      year         = {2025},
      note         = {2025 Apr 20;43(12):1463-1473},
      abstract     = {The FIRE-4 study randomly assigned patients with first-line
                      RAS wild-type (RASwt) metastatic colorectal cancer to either
                      flourouracil (FU), folinic acid, and irinotecan (FOLFIRI)
                      plus cetuximab until progression or intolerable toxicity
                      (standard arm) or to FOLFIRI plus cetuximab followed by a
                      switch maintenance treatment using FU plus bevacizumab
                      (experimental arm). Here, we investigate the relevance of
                      liquid biopsy (LB) RAS and BRAF testing compared with
                      tissue-based analyses.LBs were taken at baseline and during
                      treatment and were analyzed for RAS and BRAFV600E mutations
                      using the in vitro diagnostics-certified ONCOBEAM RAS
                      procedure (Sysmex Inostics) and digital-droplet polymerase
                      chain reaction technology.Six hundred seventy-two RASwt
                      patients were randomly assigned. LBs of 540 patients were
                      evaluable at baseline. Of those, 70 $(13\%)$ were RAS mutant
                      (RASmut) and 38 $(7\%)$ BRAFV600E mutant. RASmut patients
                      had significantly shorter survival compared with RASwt
                      patients (progression-free survival [PFS], 9.0 months v 11.5
                      months; P < .001; hazard ratio [HR], 1.66; overall survival
                      [OS], 22.1 months v 33.6 months; P < .001; HR, 1.85). RASmut
                      patients had a numerically greater benefit from early switch
                      maintenance compared with continuation of FOLFIRI/cetuximab
                      (PFS, 10.1 months v 6.4 months; HR, 0.82; OS, 24.9 months v
                      16.3 months; HR, 0.57). Patients with a BRAFV600E mutation
                      in LB showed poor outcome (PFS, 5.4 months; OS, 12.0
                      months). On the basis of serial LB analyses, the conversion
                      rate from RASwt to RASmut at disease progression was
                      significantly higher in the arm with continuous cetuximab
                      administration than in the switch maintenance arm.LB allows
                      the detection of RAS and BRAF mutations in patients deemed
                      RASwt on the basis of tissue analyses. These patients show
                      outcome characteristics expected for RAS- and BRAF-mutant
                      patients in tissue. The study thus confirms the high
                      clinical relevance of LB performed at baseline before the
                      start of therapy.},
      cin          = {BE01 / MU01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331 / I:(DE-He78)MU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39903881},
      doi          = {10.1200/JCO.24.01174},
      url          = {https://inrepo02.dkfz.de/record/298573},
}