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 ²³ Martin Kaatz ²⁴ Sebastian Haferkamp ²⁵ Ulrike Leiter ¹ Selma Ugurel ²⁶ Michael Weichenthal ² Carola Berking ²⁷ Ralf Gutzmer ²⁸ Dirk Schadendorf ²⁶ Lena Nanz ²⁹ Carmen Loquai ³⁰

• ¹ Department of Dermatology, University Hospital and Faculty of Medicine, University of Tübingen, Tuebingen, Germany
• ² Department of Dermatology, Venerology and Allergology, Faculty of Medicine, University of Kiel, Kiel, Schleswig-Holstein, Germany
• ³ Department of Dermatology and Allergology, Philipps-University Marburg, Marburg, Hesse, Germany
• ⁴ Department of Dermatology, University of Lübeck, Lübeck, Schleswig-Holstein, Germany
• ⁵ Dermatological Sciences, University of Manchester, Manchester, United Kingdom
• ⁶ Department of Dermatology, University Hospital Münster, Münster, North Rhine-Westphalia, Germany
• ⁷ Department of Dermatology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
• ⁸ Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Lower Saxony, Germany
• ⁹ Department of Palliative Medicine, Medical Faculty RWTH Aachen University, Aachen, Germany
• ¹⁰ Department of Dermatology, University Hospital Giessen, Giessen, Germany
• ¹¹ Department of Dermatology, University Hospital Carl Gustav Carus, Dresden, Lower Saxony, Germany
• ¹² Department of Dermatology, Hospital of Bremerhaven, Bremerhaven, Germany
• ¹³ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Dermatology, Venereology and Allergology, Berlin, Germany
• ¹⁴ Department of Dermatology, Helios Klinikum Erfurt, Erfurt, Germany
• ¹⁵ Department of Dermatology, University Hospital Würzburg, Würzburg, Germany
• ¹⁶ Elbe Kliniken, Buxtehude, Germany
• ¹⁷ Skin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany
• ¹⁸ Skin Cancer Unit, German Cancer Research Center, Heidelberg, Baden-Württemberg, Germany
• ¹⁹ Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany
• ²⁰ DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany
• ²¹ Department of Dermatology, Venereology and Allergology, Saarland University Hospital, Homburg, Germany
• ²² Department of Dermatology, Skin Cancer Center Harz Clinics, Quedlinburg, Germany
• ²³ Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Lübeck, Schleswig-Holstein, Germany
• ²⁴ SRH Wald-Klinikum Gera GmbH, Gera, Germany
• ²⁵ Department of Dermatology, University Hospital Regensburg, Regensburg, Bavaria, Germany
• ²⁶ Essen University Hospital, West German Cancer Center, University of Duisburg-Essen and the German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Essen, Germany
• ²⁷ Department of Dermatology, Uniklinikum Erlangen, CCC Erlangen-EMN, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany
• ²⁸ Department of Dermatology, Muehlenkreiskliniken Minden and Ruhr University Bochum, Minden, Germany
• ²⁹ Department of Dermatology, University Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany
• ³⁰ Department of Dermatology, Gesundheit Nord Klinikverbund Bremen, Bremen, Germany

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 tumour 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