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@ARTICLE{Schumann:300825,
      author       = {K. Schumann$^*$ and K. C. Klespe and C. Mauch and C. Loquai
                      and U. Schultheis and S. Börger and A. Thiem and S. Emmert
                      and M. Hoellwerth and P. Koelbinger and V. A. Nguyen and M.
                      Wanner and E. Richtig and W. K. Peitsch and W. Harth and V.
                      Zenderowski and A. D. Braun and M. Mengoni and R. Dummer and
                      J. Mangana and L. V. Maul and F. Meis and K. Rappersberger
                      and O. D. Persa$^*$ and T. Biedermann$^*$ and C. Posch$^*$},
      title        = {{S}witching {PD}-1 to {BRAF} + {MEK} inhibition improves
                      recurrence-free survival in patients receiving a second
                      course of adjuvant melanoma therapy.},
      journal      = {Journal of the European Academy of Dermatology and
                      Venereology},
      volume       = {nn},
      issn         = {0926-9959},
      address      = {Oxford [u.a.]},
      publisher    = {Wiley-Blackwell},
      reportid     = {DKFZ-2025-00939},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {PD-1 or BRAF + MEK inhibition is considered the current
                      gold standard in adjuvant melanoma therapy. Little is known
                      if, after the recurrence of the disease and surgery, a
                      second course of adjuvant therapy might be beneficial.A
                      multicenter, retrospective study investigating a second
                      course of adjuvant therapy after recurrence and surgery in
                      stage III-IV melanoma patients. Patients received nivolumab
                      (NIV), pembrolizumab (PEM) or dabrafenib plus trametinib (D
                      + T) between 01/2017 and 10/2021. The primary endpoint was
                      12-month recurrence-free survival (RFS2). Further analyses
                      included descriptive and correlative statistics.Sixty-six
                      patients from 22 centers in Germany, Austria and Switzerland
                      were included. Thirty-two patients received D + T as
                      second-course adjuvant therapy, 9 patients received PEM and
                      25 patients received NIV. Recurrence-free survival for the
                      second-course adjuvant treatment (RFS2) was assessed after
                      12 and 24 months and showed a superiority of adjuvant BRAF +
                      MEK over PD-1 therapy (12-months RFS2: $90.6\%$ vs.
                      $70.6\%,$ HR 4.226 $[95\%$ CI 1.154-15.48]; p = 0.030;
                      24-months RFS2 $71.9\%$ vs. $52.9\%,$ HR 3.154 $[95\%$ CI
                      1.374-7.242]; p = 0.007). There was no significant decrease
                      in OS with either BRAF + MEK or PD-1 treatment (12-months
                      OS: $100\%$ both, 24-months OS: $100\%$ vs. $93.8\%).$
                      Furthermore, therapy sequences were investigated. For better
                      comparability, only BRAF V600 mutated patients were
                      assessed: RFS2 was significantly better for patients with a
                      class switch from PD-1 to BRAF + MEK compared to BRAF + MEK
                      to PD-1 (HR 4.401 (1.04-18.63), p = 0.044). No new safety
                      signals were detected.In the investigated cohort, a second
                      course of adjuvant melanoma treatment is feasible and
                      provides similar RFS compared to an initial course of
                      adjuvant therapy using BRAF + MEK inhibitors; however, RFS2
                      is reduced for PD-1 antibodies. In addition, both treatments
                      were convincing with a 24-month OS of almost $100\%.$
                      Switching from adjuvant PD-1 to BRAF + MEK treatment
                      provided better overall RFS compared to switching from
                      adjuvant BRAF + MEK to PD-1 treatment.},
      cin          = {MU01},
      ddc          = {610},
      cid          = {I:(DE-He78)MU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40331873},
      doi          = {10.1111/jdv.20708},
      url          = {https://inrepo02.dkfz.de/record/300825},
}