Influence of adjuvant therapies on organ-specific recurrence of cutaneous melanoma: a multicenter study on 1383 patients of the prospective DeCOG registry ADOReg : cancer therapy and prevention

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 extra...

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Main Authors: Wohlfeil, Sebastian A. (Author) , Kranzmann, Leonie (Author) , Weiß, Christel (Author) , von Wasielewski, Imke (Author) , Klespe, Kai C. (Author) , Kähler, Katharina C. (Author) , Weichenthal, Michael (Author) , Schadendorf, Dirk (Author) , Zimmer, Lisa (Author) , Mohr, Peter (Author) , Meier, Friedegund (Author) , Pfoehler, Claudia (Author) , Berking, Carola (Author) , Heppt, Markus V. (Author) , Herbst, Rudolf (Author) , Kreuter, Alexander (Author) , Gutzmer, Ralf (Author) , Ulrich, Jens (Author) , Meiss, Frank (Author) , Gebhardt, Christoffer (Author) , Dippel, Edgar (Author) , Leiter, Ulrike (Author) , Schilling, Bastian (Author) , Ugurel, Selma (Author) , Utikal, Jochen (Author)
Format: Article (Journal)
Language:English
Published: 15 November 2024
In: International journal of cancer
Year: 2024, Volume: 155, Issue: 10, Pages: 1808-1823
ISSN:1097-0215
DOI:10.1002/ijc.35078
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ijc.35078
Verlag, kostenfrei, Volltext: http://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.35078
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Author Notes:Sebastian A. Wohlfeil, Leonie Kranzmann, Christel Weiß, Imke von Wasielewski, Kai C. Klespe, Katharina C. Kähler, Michael Weichenthal, Dirk Schadendorf, Lisa Zimmer, Peter Mohr, Friedegund Meier, Claudia Pfoehler, Carola Berking, Markus V. Heppt, Rudolf Herbst, Alexander Kreuter, Ralf Gutzmer, Jens Ulrich, Frank Meiss, Christoffer Gebhardt, Edgar Dippel, Ulrike Leiter, Bastian Schilling, Selma Ugurel, Jochen Utikal

MARC

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520 |a 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. 
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