Influence of adjuvant therapies on organ-specific recurrence of cutaneous melanoma: A multicenter study on 1383 patients of the prospective DeCOG registry ADOReg

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Sebastian A. Wohlfeil - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Leonie Kranzmann - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Christel Weiß - , Heidelberg University  (Author)
  • Imke von Wasielewski - , Hannover Medical School (MHH) (Author)
  • Kai C. Klespe - , Hannover Medical School (MHH) (Author)
  • Katharina C. Kähler - , University Hospital Schleswig-Holstein Campus Kiel (Author)
  • Michael Weichenthal - , University Hospital Schleswig-Holstein Campus Kiel (Author)
  • Dirk Schadendorf - , German Cancer Research Center (DKFZ) (Author)
  • Lisa Zimmer - , German Cancer Research Center (DKFZ) (Author)
  • Peter Mohr - , Elbe Clinics Stade/Buxtehude (Author)
  • Friedegund Meier - , Department of Dermatology, Skin Tumor Center, University Hospital Carl Gustav Carus Dresden (Author)
  • Claudia Pfoehler - , Saarland University (Author)
  • Carola Berking - , Friedrich-Alexander University Erlangen-Nürnberg, University Hospital at the Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Markus V. Heppt - , Friedrich-Alexander University Erlangen-Nürnberg, University Hospital at the Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Rudolf Herbst - , Fresenius AG (Author)
  • Alexander Kreuter - , Witten/Herdecke University (Author)
  • Ralf Gutzmer - , Ruhr University Bochum (Author)
  • Jens Ulrich - , Otto von Guericke University Magdeburg (Author)
  • Frank Meiss - , University Medical Center Freiburg (Author)
  • Christoffer Gebhardt - , University of Hamburg (Author)
  • Edgar Dippel - , Klinikum Ludwigshafen (Author)
  • Ulrike Leiter - , University of Tübingen (Author)
  • Bastian Schilling - , University of Würzburg, University Hospital Frankfurt (Author)
  • Selma Ugurel - , German Cancer Research Center (DKFZ) (Author)
  • Jochen Utikal - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)

Abstract

This study investigated whether adjuvant treatments in stage III cutaneous melanoma (CM) influenced patterns of recurrence. Patients with primary (n = 1033) or relapsed CM (n = 350) who received adjuvant therapies with Nivolumab (N), Pembrolizumab (P), or Dabrafenib and Trametinib (D + T) were extracted from the prospective multicenter real-world skin cancer registry ADOReg. Endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), organ-specific DMFS, and overall survival (OS). For primary cases, D + T indicated an improved PFS (1- and 2-year PFS: 90.9%; 82.7%) as compared to P (81.0%, 73.9%; p =.0208), or N (83.8%, 75.2%; p =.0539). BRAF-mutated(mut) CM demonstrated significantly lower PFS (p =.0022) and decreased DMFS (p =.0580) when treated with immune checkpoint inhibitor (ICI) instead of D + T. Besides, NRAS-mut CM tended to perform worse than wt CM upon ICI (PFS: p =.1349; DMFS: p =.0540). OS was similar between the groups. Relapsed cases showed decreased PFS, DMFS, and OS in comparison to primary (all: p <.001), without significant differences between the subgroups. Organ-specific DMFS was significantly altered for primary cases with bone (p =.0367) or brain metastases (p =.0202). In relapsed CM, the frequency of liver (D + T: 1.5%; P: 12%; N: 9%) and LN metastases (D + T: 1.5%; P: 12%; N: 10.2%) was significantly lower with adjuvant D + T than ICI. NRAS-mut CM showed increased recurrence in primary and relapsed cases. These data show that adjuvant D + T is superior to ICI in primary BRAF-mut CM.

Details

Original languageEnglish
JournalInternational journal of cancer
Publication statusAccepted/In press - 2024
Peer-reviewedYes

Keywords

ASJC Scopus subject areas

Keywords

  • adjuvant treatment, immune checkpoint inhibition, melanoma, targeted therapy, therapy resistance