Impact of osteoprotective therapies on the efficacy of immune checkpoint inhibition in melanoma patients – A multicentre study from the prospective skin cancer registry ADOReg

<h2>Abstract</h2><h3>Background</h3> Osteoprotective therapy (OT), including denosumab and bisphosphonates, is approved as supportive treatment for patients with solid tumors to prevent skeletal-related events from bone metastases. Preclinical studies and clinical studies/series suggested a synergistic effect of OT and immune checkpoint inhibitor (ICI) therapy in metastatic melanoma patients with bone metastases. Therefore, we investigated this issue in a registry study. <h3>Methods</h3> Melanoma patients with bone metastases undergoing first-line therapy with ICI were retrospectively identified from the prospective skin cancer registry ADOReg. Information on OT was additionally requested from the participating centers. The primary study endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and time to next treatment (TTNT). <h3>Results</h3> 180 patients were identified and analysed. Of those, 107 patients (59.4 %) received PD-1 monotherapy and 73 (40.6 %) dual ICI therapy (PD-1 + CTLA-4). 64 patients received additional an OT therapy (36 %) (OT<sub>pos</sub>). The median follow-up was 22.6 months (95 % CI=18.2–27.1). There were no significant differences in demographics or clinical parameters between OT<sub>pos</sub> and OT<sub>neg</sub> patients. The DCR was comparable between groups (p = 0.758; OT<sub>pos</sub> = 23.3 % (95 % CI=12.7–35.1), OT<sub>neg</sub> = 25.5 % (95 % CI=17.0–35.2)). There was no significant difference observed between groups in PFS (p = 0.489; OT<sub>pos</sub> = 6.7 months (95 % CI=1.3–12.1), OT<sub>neg</sub> = 6.4 months (95 % CI=1.9–11.0)), in OS (p = 0.065; OT<sub>pos</sub> = 26.1 months (95 % CI=14.6–37.5), OT<sub>neg</sub> = 16.9 months (95 % CI=6.2–27.6)) and in TTNT (p = 0.891; OT<sub>pos</sub> = 18.4 months (95 % CI=10.9–25.9), OT<sub>neg</sub> = 21.5 months (95 % CI=7.8–35.1)). <h3>Summary</h3> The majority of melanoma patients with bone metastasis did not receive an OT. No significant effects of OT were observed on efficacy outcomes, including response, PFS, OS, and TTNT.

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Publication Details

Journal
EJC Skin Cancer
Published
2025-01-01
DOI
https://doi.org/10.1016/j.ejcskn.2025.100731
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
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article

Impact of osteoprotective therapies on the efficacy of immune checkpoint inhibition in melanoma patients – A multicentre study from the prospective skin cancer registry ADOReg

Patrick Terheyden, Ralf Gutzmer, Yenny Angela, Michael Weichenthal et al.
EJC Skin Cancer
Cancer Immunotherapy and Biomarkers
article

Impact of osteoprotective therapies on the efficacy of immune checkpoint inhibition in melanoma patients – A multicentre study from the prospective skin cancer registry ADOReg

Patrick Terheyden, Ralf Gutzmer, Yenny Angela, Michael Weichenthal, Claudia Pföhler, Sebastian Haferkamp, Corinna Kochanek, Katrin Schaper‐Gerhardt, Dirk Schadendorf, Friedegund Meier, Peter Mohr, Selma Ugurel, Frank Meiß, Lisa Zimmer, Ulrike Leiter, Martin Kaatz, Michael Sachse, Jens Ulrich, Imke von Wasielewski
article en

Abstract

<h2>Abstract</h2><h3>Background</h3> Osteoprotective therapy (OT), including denosumab and bisphosphonates, is approved as supportive treatment for patients with solid tumors to prevent skeletal-related events from bone metastases. Preclinical studies and clinical studies/series suggested a synergistic effect of OT and immune checkpoint inhibitor (ICI) therapy in metastatic melanoma patients with bone metastases. Therefore, we investigated this issue in a registry study. <h3>Methods</h3> Melanoma patients with bone metastases undergoing first-line therapy with ICI were retrospectively identified from the prospective skin cancer registry ADOReg. Information on OT was additionally requested from the participating centers. The primary study endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and time to next treatment (TTNT). <h3>Results</h3> 180 patients were identified and analysed. Of those, 107 patients (59.4 %) received PD-1 monotherapy and 73 (40.6 %) dual ICI therapy (PD-1 + CTLA-4). 64 patients received additional an OT therapy (36 %) (OT<sub>pos</sub>). The median follow-up was 22.6 months (95 % CI=18.2–27.1). There were no significant differences in demographics or clinical parameters between OT<sub>pos</sub> and OT<sub>neg</sub> patients. The DCR was comparable between groups (p = 0.758; OT<sub>pos</sub> = 23.3 % (95 % CI=12.7–35.1), OT<sub>neg</sub> = 25.5 % (95 % CI=17.0–35.2)). There was no significant difference observed between groups in PFS (p = 0.489; OT<sub>pos</sub> = 6.7 months (95 % CI=1.3–12.1), OT<sub>neg</sub> = 6.4 months (95 % CI=1.9–11.0)), in OS (p = 0.065; OT<sub>pos</sub> = 26.1 months (95 % CI=14.6–37.5), OT<sub>neg</sub> = 16.9 months (95 % CI=6.2–27.6)) and in TTNT (p = 0.891; OT<sub>pos</sub> = 18.4 months (95 % CI=10.9–25.9), OT<sub>neg</sub> = 21.5 months (95 % CI=7.8–35.1)). <h3>Summary</h3> The majority of melanoma patients with bone metastasis did not receive an OT. No significant effects of OT were observed on efficacy outcomes, including response, PFS, OS, and TTNT.

EJC Skin CancerVol. 3
University of Freiburg (DE), Skin Cancer Foundation (US), University Hospital Regensburg (DE), Medizinische Hochschule Hannover (DE), Düsseldorf University Hospital (DE), SRH Wald-Klinikum Gera (DE), National Center for Tumor Diseases (DE), University Hospital Schleswig-Holstein (DE), Essen University Hospital (DE), Elbe Kliniken Stade-Buxtehude (DE), Klinikum Bremerhaven-Reinkenheide (DE), West German Heart and Vascular Center Essen (DE), University Hospital Carl Gustav Carus (DE), Klinikum Chemnitz (DE), Johannes Wesling Klinikum Minden (DE), Heinrich Heine University Düsseldorf (DE), Technische Universität Dresden (DE), University of Tübingen (DE), Ruhr University Bochum (DE), Saarland University (DE), University of Lübeck (DE)
Amgen, Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Sanofi, Regeneron Pharmaceuticals, Les Laboratories Pierre Fabre, Innovent Biologics, Sun Pharma, NeraCare, InflaRx
Good health and well-being
Openalex Percentile: Top 89%
Cancer Immunotherapy and Biomarkers
DOIOpen Access PDFOpenAlex
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