Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2025 Feb 24:16:1509886.
doi: 10.3389/fimmu.2025.1509886. eCollection 2025.

Treatment at the end of life in patients with advanced melanoma. A multicenter DeCOG study of 1067 patients from the prospective skin cancer registry ADOReg

Andrea Forschner  1 , Katharina C Kähler  2 , Martin Gschnell  3 , Ewan A Langan  4   5 , Carsten Weishaupt  6 , Frank Meiss  7 , Kai-Martin Thoms  8 , Renate U Wahl  9 , Daniela Göppner  10 , Marlene Garzarolli  11 , Michael Sachse  12 , Max Schlaak  13 , Markus Reitmajer  1 , Ivonne Kellner  14 , Anja Gesierich  15 , Peter Mohr  16 , Friedegund Meier  11 , Imke von Wasielewski  17 , Rudolf Herbst  14 , Jochen Utikal  18   19   20 , Claudia Pföhler  21 , Jens Ulrich  22 , Patrick Terheyden  4 , Martin Kaatz  23 , Sebastian Haferkamp  24 , Ulrike Leiter  1 , Selma Ugurel  25 , Michael Weichenthal  2 , Carola Berking  26 , Ralf Gutzmer  27 , Dirk Schadendorf  25 , Lena Nanz #  1 , Carmen Loquai #  28
Affiliations
Multicenter Study

Treatment at the end of life in patients with advanced melanoma. A multicenter DeCOG study of 1067 patients from the prospective skin cancer registry ADOReg

Andrea Forschner et al. Front Immunol. .

Abstract

Background: Although systemic therapies have improved considerably over the last decade, up to 50% of patients with metastatic melanoma still die due to disease progression. Oncological treatment at the end-of-life phase is challenging. The aim of this study was to investigate the frequency and type of systemic therapy received by melanoma patients in their end-of-life phase.

Methods: Patients with metastatic melanoma who had died between January 1, 2018 and October 31, 2022 were identified from the prospective multicenter skin cancer registry ADOReg. Study endpoints were percentage of patients who had been treated with systemic therapy within the last three months of life, timepoint of initiation of the last-line therapy, overall survival, treatment benefit and the incidence of treatment-related adverse events.

Results: In total, 1067 patients from 46 skin cancer centers were included. Most of the patients (63%) had received immune checkpoint inhibitors (ICI) as last-line therapy, 22% targeted therapies (TT) and 12% chemotherapy (CTX). Comparing last-line ICI and TT, patients with TT were significantly more likely to benefit from treatment and had significantly fewer and milder treatment-related AE than patients with ICI. Even though two thirds of patients had received ICI as a last-line therapy, the majority of these patients (61%) had stopped therapy within the last 30 days of life, whereas the majority of patients with TT (66%) still continued their treatment to the end of life. We found markedly fewer patients with initiation of ICI within 30 days before their death (19%) compared to a historic cohort including patients who died in 2016 or 2017 (39%).

Conclusion: Treatment approaches near the end of life have markedly changed in skin cancer centers in Germany over recent years, with ICI prescribed less frequently in the end-of-life phase. In contrast, TT are frequently administered, even within the last 30 days of life. It should also be considered that discontinuation of TT can result in rapid tumor progression. Due to the oral administration and a low rate of severe toxicity, TT appear to be a suitable treatment option, even in the end-of-life situation of melanoma patients.

Keywords: BRAF and MEK inhibitors; end of life; immune checkpoint inhibitors; ipilimumab; melanoma; nivolumab.

PubMed Disclaimer

Conflict of interest statement

AF: served as a consultant to Novartis, MSD, BMS, Pierre-Fabre and Immunocore; received travel support from Novartis, BMS, Pierre-Fabre, MSD, received speaker fees from Novartis, Delcath, BMS and MSD and reports institutional research grants from BMS Stiftung Immunonkologie. KK: Honoraria: BMS, MSD, Novartis, Sanofi-Aventis, Immunocore, Philogen, Consulting or Advisory Role: BMS, MSD, Pierre Fabre, Philogen, Sun Pharma, Speakers’ Bureau: No Relationships to Disclose, Research Funding: Novartis,Travel, Accommodations, Expenses: BMS, MSD, Novartis, Roche, Pierre Fabre,Sun Pharma. MGs Honoraria for lectures/advisory boards BristolMyers Squibb, MerckSharpDohme, Merck-Serono, Almirall Hermal, Sun Pharma, Delcath, Sanofi/Regeneron and travel support from Almirall Hermal and Pierre Fabre, outside the submitted work. EL Honoraria for lectures/advisory boards BristolMyers Squibb, Novartis, Sun Pharma outside the submitted work. FraM served as consultant and/or has received honoraria from Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, Sanofi Genzyme, Sun Pharma and travel support from Novartis, Sun Pharma, Pierre Fabre and Merck Sharp & Dohme, outside the submitted work. K-MT received honoraria for lectures or advisory boards from Bristol Myers Squibb, MSD, Pierre Fabre, Novartis, Roche, Immunocore, Sanofi, Sun Pharma, Amgen, LEO Pharma, Galderma, Almirall, Candela and Lilly. DG served as a consultant to Novartis, Pierre-Fabre, Bristol Myers Squibb, MSD Sharp & Dohme, Sun Pharma, Sanofi, Immunocore and Janssen; received travel and conference support from Pierre-Fabre, Kyowa Kirin and Sun Pharma, received speaker fees from Janssen and Sun Pharma. MGa reports honoraria and travel support from Amgen, Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, Roche, and Sanofi. MSc Advisory boards of Bristol-Myers Squibb, Novartis, MSD, Pierre Fabre, Kyowa Kirin, Immunocore, and Sanofi-Genzyme. Travel accommodation and expenses by Novartis, Pierre Fabre, and Sun Pharma. MR received a funding as part of the Clinician Scientists Program of the University of Tübingen (application no. 523-0-0) and travel support from Almirall Hermal and Pierre Fabre, outside the submitted work. IK is employee of Helios Klinikum Erfurt GmbH. AG served as consultant and/or has received honoraria or travel costs from Allmiral, Amgen, Bristol-Myers Squibb, Immunocore, MSD Sharp & Dohme; Novartis, Pierre Fabre Pharmaceuticals, Pfizer, Roche and Sanofi Genzyme, outside the submitted work. PM reports institutional grants from Bristol Myers Squibb, MSD, and Novartis; personal fees and honoraria from Amgen, Bristol Myers Squibb, GSK, MSD, Merck Serono, Novartis, Pierre Fabre, Roche, Sanofi, and Sun Pharma; and travel support from Bristol Myers Squibb. PM participated on a data safety monitoring or advisory board from Almirall Hermal, Amgen, Beiersdorf, Bristol Myers Squibb, MSD, Merck Serono, Novartis, Pierre Fabre, Roche, Sanofi, and Sun Pharma, and received travel support from Bristol Myers Squibb and Sun Pharma. FriM reports consulting fees and honoraria and participation on a drug safety monitoring or advisory board for Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, Roche, and Sanofi, and support for attending meetings or travel grants from Bristol Myers Squibb, MSD, Pierre Fabre, and Sanofi. IV received honoraria for lectures or advisory boards from Bristol Myers Squibb, MSD, Pierre Fabre, Novartis, Regeneron, Sanofi and Stemline. RH is employee of Helios Klinikum Erfurt GmbH. JUt is on the advisory board or has received honoraria and travel support from Amgen, Bristol Myers Squibb, GSK, Immunocore, LeoPharma, Merck Sharp and Dohme, Novartis, Pierre Fabre, Rheacell, Roche, Sanofi outside the submitted work. CP served as consultant and/or has received honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Sanofi, Sunpharma, Pierre Fabre, AbbVie, Kyona Kirin and Amgen and received travel support from Amgen, Merck Sharp & Dohme , Bristol-Myers Squibb , Pierre Fabre, Sunpharma and Novartis, outside the submitted work. JUl served as a consultant to BMS, Sun Pharma, and Regeneron; received speaker fees from BMS, MSD, Novartis, Pierre-Fabre, Sanofi, Regeneron and Sun Pharma. PT served as consultant and/or received honoraria form Almirall, Bristol Myers Squibb, Biofrontera, Kyowa Kirin, L’Oréal, Merck Sharp & Dohme, Novartis, Pierre-Fabre, Sanofi, 4SC, and travel support from Bristol Myers Squibb outside the submitted work. MK Honoraria for lectures/advisory boards, studies: BMS, Sunpharma, MSD, Novartis, Immunocore, Regeneron, Pierre Fabre. SH Honoraria for lectures/advisory boards BristolMyers Squibb, MerckSharpDohme, Novartis, Pierre-Fabre, Sun Pharma, Immunocore, Sanofi/Regeneron UL served as a consultant to Novartis, MSD, Sun Pharma, Sanofi and Regeneron; received travel support from Pierre-Fabre and Sun Pharma, received speaker fees from Sanofi, Regeneron and Sun Pharma, and reports institutional research grants from MSD. SU declares research support from Bristol Myers Squibb and Merck Serono; speakers and advisory board honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, and Novartis; and meeting and travel support from Almirall, Bristol-Myers Squibb, IGEA Clinical Biophysics, Merck Sharp & Dohme, Novartis, Pierre Fabre, and Sun Pharma. CB Honoraria for lectures/advisory boards from Bristol Myers Squibb, Merck Sharp Dohme, Novartis, Almirall Hermal, Leo Pharma, Pierre Fabre, InflaRx, Immunocore, Delcath, Sanofi, Regeneron; RG: Honoraria for lectures/advisory boards BristolMyers Squibb, MerckSharpDohme, Novartis, Merck-Serono, Amgen, Almirall Hermal, Pierre-Fabre, Sun Pharma, Immunocore, 4SC, Delcath, Sanofi/Regeneron; Meeting support SUN Pharma, Boehringer Ingelheim, PierreFabre; Research support (to institution) Novartis, Sanofi/Regeneron, Merck Serono, Amgen, SUN Pharma, KyowaKirin, Almirall Hermal. DS a member of the advisory board, consultant or received speakers´ honoraria from: Astra Zeneca, BMS, CureVac, Daiichi Sankyo, Erasca, Haystack, Immatics, Immunocore, InFlarX, Lapcorp, Merck-Serono, MSD, Neracare, Novartis, Novogenix, PamGene, Philogen, Pierre Fabre, Pfizer, Regeneron, Replimune, Sanofi, Seagen, Sun Pharma, UltraVacs; research funding from BMS, Roche, MSD, Amgen & Novartis. CL Advisory Board: BMS, MSD, Merck, Roche, Immunocore, Novartis, Pierre Fabre, Sanofi, Sun Pharma, Almirall Hermal, Kyowa Kirin, Biontech. Speakers fee: BMS, MSD, Merck, Roche, Immunocore, Novartis, Pierre Fabre, Sanofi, Sun Pharma, Almirall Hermal, Kyowa Kirin, Biontech. Travel reimbursement: BMS, MSD, Merck, Roche, Immunocore, Novartis, Pierre Fabre, Sanofi, Sun Pharma, Almirall Hermal, Kyowa Kirin, Biontech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overall survival since treatment initiation of last-line systemic therapy. ICI, immune checkpoint inhibitors; TT, Targeted therapies; CTX, Chemotherapy.
Figure 2
Figure 2
Treatment benefit and toxicity of last-line ICI (green, left part) and TT (blue, right part).
See this image and copyright information in PMC

References

    1. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. . Improved survival with ipilimumab in patients with metastatic melanoma. New Engl J Med. (2010) 363:711–23. doi: 10.1056/NEJMoa1003466 - DOI - PMC - PubMed
    1. Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. . Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. (2014) 371:1877–88. doi: 10.1056/NEJMoa1406037 - DOI - PubMed
    1. Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, et al. . Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicenter, open-label, randomized phase 3 trial. Lancet Oncol. (2018) 19:603–15. doi: 10.1016/S1470-2045(18)30142-6 - DOI - PubMed
    1. van Lith PEA, Schreuder K, Jalving M, Reyners AKL, Been LB, Rácz E, et al. . Systemic therapy timing and use in patients with advanced melanoma at the end of life: A retrospective cohort study. J Dermatol. (2024) 51:584–91. doi: 10.1111/1346-8138.17061 - DOI - PMC - PubMed
    1. van Breeschoten J, Ismail RK, Wouters M, Hilarius DL, de Wreede LC, Haanen JB, et al. . End-of-life use of systemic therapy in patients with advanced melanoma: A nationwide cohort study. JCO Oncol Pract. (2022) 18:e1611–e20. doi: 10.1200/OP.22.00061 - DOI - PubMed

Publication types

MeSH terms

Substances