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@ARTICLE{Haist:282917,
      author       = {M. Haist and H. Stege and F. Rogall and Y. Tan and I. von
                      Wasielewski and K. C. Klespe and F. Meier and P. Mohr and K.
                      C. Kähler and M. Weichenthal and A. Hauschild and D.
                      Schadendorf$^*$ and S. Ugurel$^*$ and G. Lodde$^*$ and L.
                      Zimmer$^*$ and R. Gutzmer and D. Debus and B. Schilling and
                      A. Kreuter and J. Ulrich and F. Meiss and R. Herbst and A.
                      Forschner and U. Leiter and C. Pfoehler and M. Kaatz and F.
                      Ziller and J. C. Hassel and M. Tronnier and M. Sachse and E.
                      Dippel and P. Terheyden and C. Berking and M. V. Heppt and
                      F. Kiecker and S. Haferkamp and C. Gebhardt and J. C. Simon
                      and S. Grabbe and C. Loquai},
      title        = {{T}reatment management for {BRAF}-mutant melanoma patients
                      with tumor recurrence on adjuvant therapy: a multicenter
                      study from the prospective skin cancer registry {ADOREG}.},
      journal      = {Journal for ImmunoTherapy of Cancer},
      volume       = {11},
      number       = {9},
      issn         = {2051-1426},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2023-01906},
      pages        = {e007630},
      year         = {2023},
      abstract     = {Adjuvant therapy with immune-checkpoint inhibitors (CPI) or
                      BRAF/MEK-directed targeted therapy (TT) improves
                      recurrence-free survival (RFS) for patients with advanced,
                      BRAFV600-mutant (BRAFmut) resected melanoma. However, $40\%$
                      of these patients will develop distant metastases (DM)
                      within 5 years, which require systemic therapy. Little data
                      exist to guide the choice of upfront adjuvant therapy or
                      treatment management upon DM. This study evaluated the
                      efficacy of subsequent treatments following tumor recurrence
                      upon upfront adjuvant therapy.For this multicenter cohort
                      study, we identified 515 BRAFmut patients with resected
                      stage III melanoma who were treated with PD-1 inhibitors
                      (anti-PD1) or TT in the adjuvant setting. Disease
                      characteristics, treatment regimens, details on tumor
                      recurrence, subsequent treatment management, and survival
                      outcomes were collected within the prospective, real-world
                      skin cancer registry ADOReg. Primary endpoints included
                      progression-free survival (PFS) following DM and best tumor
                      response to first-line (1L) treatments.Among 515 eligible
                      patients, 273 patients received adjuvant anti-PD1 and 242
                      adjuvant TT. At a median follow-up of 21 months, $54.6\%$ of
                      anti-PD1 patients and $36.4\%$ of TT patients recurred,
                      while $39.6\%$ (anti-PD1) and $29.3\%$ (TT) developed DM.
                      Risk of recurrence was significantly reduced in patients
                      treated with TT compared with anti-PD1 (adjusted HR 0.52;
                      $95\%$ CI 0.40 to 0.68, p<0.001). Likewise, median RFS was
                      significantly longer in TT-treated patients (31 vs 17
                      months, p<0.001). Patients who received TT as second
                      adjuvant treatment upon locoregional recurrence had a longer
                      RFS2 as compared with adjuvant CPI (41 vs 6 months,
                      p=0.009). Patients who recurred at distant sites following
                      adjuvant TT showed favorable response rates $(42.9\%)$ after
                      switching to 1L ipilimumab+nivolumab (ipi+nivo). Patients
                      with DM during adjuvant anti-PD1 achieved response rates of
                      $58.7\%$ after switching to 1L TT and $35.3\%$ for 1L
                      ipi+nivo. Overall, median PFS was significantly longer in
                      patients who switched treatments for stage IV disease
                      (median PFS 9 vs 5 months, p=0.004).BRAFmut melanoma
                      patients who developed DM upon upfront adjuvant therapy
                      achieve favorable tumor control and prolonged PFS after
                      switching treatment modalities in the first-line setting of
                      stage IV disease. Patients with locoregional recurrence
                      benefit from complete resection of recurrence followed by a
                      second adjuvant treatment with TT.},
      keywords     = {Adjuvant Drug Therapy (Other) / Immune Checkpoint
                      Inhibitors (Other) / Melanoma (Other) / Molecular Targeted
                      Therapy (Other) / Recurrence (Other)},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37730278},
      doi          = {10.1136/jitc-2023-007630},
      url          = {https://inrepo02.dkfz.de/record/282917},
}