Synergistic effect between denosumab and immune checkpoint inhibitors (ICI)? A retrospective study of 268 patients with ICI and bone metastases

• Published in: Journal of bone oncology 2024-10, Vol.48, p.100634, Article 100634
• Main Authors: Mabrut, E., Mainbourg, S., Peron, J., Maillet, D., Dalle, S., Fontaine Delaruelle, C., Grolleau, E., Clezardin, P., Bonnelye, E., Confavreux, C.B., Massy, E.
• Format: Article
• Language: English
• Subjects: Bone metastasis; Denosumab; Immune check point inhibitors; Life Sciences; Research Paper; Survival
• ISSN: 2212-1374; 2212-1366; 2212-1374
• DOI: 10.1016/j.jbo.2024.100634

•Bone metastasis significantly affects patient survival and quality of life in advanced solid tumors, and denosumab is used to prevent skeletal-related events in these cases.•The study investigates the potential synergistic effects of combining immunotherapy with denosumab, leveraging anecdotal evidence and preliminary research.•A retrospective analysis was conducted on patients with bone metastases receiving immune checkpoint inhibitors (ICI) from the IMMUCARE database.•Results indicated no significant differences in overall survival or progression-free survival between ICI monotherapy and combined ICI-denosumab treatment.•Notably, patients who received denosumab after starting ICI treatment showed a significant survival advantage, suggesting potential benefits from this sequential therapy approach. Bone metastasis is a significant concern in advanced solid tumors, contributing to diminished patient survival and quality of life due to skeletal-related events (SREs). Denosumab (DMAB), a monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand (RANKL), is used to prevent SREs in such cases. The RANK/RANKL axis, crucial in immunological processes, has garnered attention, especially with the expanding use of immune checkpoint inhibitors (ICI) in modern oncology. Our study aims to explore the potential synergistic antitumor effects of combining immunotherapy with denosumab, as suggested by anecdotal evidence, small cohort studies, and preclinical research. We conducted a retrospective analysis using the IMMUCARE database, encompassing patients receiving ICI treatment since 2014 and diagnosed with bone metastases. We examined overall survival (OS), progression-free survival (PFS) and switch of treatment line based on denosumab usage. Patients were stratified into groups: without denosumab, ICI followed by denosumab, and denosumab followed by ICI. Survival curves and multivariate Cox regression analyses were performed. Among the 268 patients with bone metastases, 154 received treatment with ICI alone, while 114 received ICI in combination with denosumab at some point during their oncological history. No significant differences were observed in overall survival (OS) or progression-free survival (PFS) between patients receiving ICI monotherapy and those receiving ICI with denosumab (p = 0.29 and p = 0.79, respectively). However, upon analyzing patients who received denosumab following ICI initiation (17 patients), a notable difference