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@ARTICLE{Stintzing:277101,
      author       = {S. Stintzing$^*$ and K. Heinrich and D. Tougeron and D. P.
                      Modest and I. Schwaner and J. Eucker and R. Pihusch and M.
                      Stauch and F. Kaiser and C. Kahl and M. Karthaus and C.
                      Müller and C. Burkart and A. Reinacher-Schick and S.
                      Kasper-Virchow and L. Fischer von Weikersthal and B.
                      Krammer-Steiner and G. W. Prager and J. Taieb and V.
                      Heinemann$^*$},
      title        = {{FOLFOXIRI} {P}lus {C}etuximab or {B}evacizumab as
                      {F}irst-{L}ine {T}reatment of {BRAFV}600{E}-{M}utant
                      {M}etastatic {C}olorectal {C}ancer: {T}he {R}andomized
                      {P}hase {II} {FIRE}-4.5 ({AIO} {KRK}0116) {S}tudy.},
      journal      = {Journal of clinical oncology},
      volume       = {41},
      number       = {25},
      issn         = {0732-183X},
      address      = {Alexandria, Va.},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2023-01266},
      pages        = {4143-4153},
      year         = {2023},
      note         = {2023 Sep 1;41(25):4143-4153},
      abstract     = {BRAFV600E mutation is associated with a poor outcome in
                      metastatic colorectal cancer (mCRC). This clinical trial
                      investigated the efficacy of triplet chemotherapy
                      (fluorouracil, folinic acid, oxaliplatin, and irinotecan)
                      combined with either cetuximab or bevacizumab in patients
                      with previously untreated BRAFV600E-mutant mCRC.In this
                      controlled, randomized, open-label phase II trial, 109
                      patients were randomly assigned, 107 of whom were included
                      into the full analysis set (FAS). Patients were randomly
                      assigned in a 2:1 ratio to receive either FOLFOXIRI plus
                      cetuximab in the experimental arm (n = 72) or FOLFOXIRI plus
                      bevacizumab in the control arm (n = 35). The primary end
                      point was objective response rate (ORR) according to RECIST
                      1.1., evaluated in patients treated according to protocol
                      (ATP population). Progression-free survival (PFS), overall
                      survival (OS), toxicity, and feasibility were analyzed as
                      secondary end points.Eighteen patients discontinued study
                      treatment before the first tumor assessment, thus resulting
                      in the ATP population of 89 patients. In these patients, ORR
                      was $51\%$ (30/59) in the cetuximab-based experimental arm
                      and $67\%$ (20/30) in the bevacizumab-based control arm
                      (odds ratio, 1.93; $80\%$ CI, 1.06 to 3.52; P = .92
                      [one-sided]). In the full analysis set, median PFS was
                      significantly inferior in the experimental arm (6.7 months v
                      10.7 months; hazard ratio [HR], 1.89; P = .006). Median OS
                      analyzed at an event rate of $64.5\%$ showed a trend toward
                      shorter survival in cetuximab-treated patients (12.9 months
                      v 17.1 months; HR, 1.4; P = .20).To our knowledge, FIRE-4.5
                      is the first prospective and randomized study investigating
                      first-line treatment of BRAFV600E-mutant mCRC. FOLFOXIRI
                      plus cetuximab does not induce a higher ORR when compared
                      with FOLFOXIRI plus bevacizumab in first-line treatment of
                      BRAFV600E-mutant mCRC. Bevacizumab-based chemotherapy
                      remains the preferable first-line treatment of patients with
                      BRAFV600E-mutant mCRC.},
      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:37352476},
      doi          = {10.1200/JCO.22.01420},
      url          = {https://inrepo02.dkfz.de/record/277101},
}