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Synergistic effect between denosumab and immune checkpoint inhibitors (ICI)? A retrospective study of 268 patients
E Mabrut1,2, S Mainbourg3, J Peron4
1Université de Lyon, France.
Background:
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.
Objective:
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.
Methods:
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.
Results:
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 emerged. The group receiving ICI followed by denosumab exhibited a significant advantage compared to those without denosumab (154 patients) or those receiving denosumab before ICI initiation (72 patients) (p = 0.022).
Conclusion:
This retrospective investigation supports the notion of potential benefits associated with sequential administration of ICI and denosumab, although statistical significance was not achieved. Future studies, including prospective trials or updated retrospective analyses, focusing on cancers treated with first-line immunotherapy, could provide further insights into this therapeutic approach.
Insights
Combining immunotherapy with denosumab may benefit patients with bone metastases when denosumab follows immune checkpoint inhibitor (ICI) treatment. This sequential approach showed improved outcomes in a retrospective analysis, warranting further investigation in prospective trials.
Area of Science:
- Oncology
- Immunotherapy
- Bone Metastasis Research
Background:
- Bone metastasis significantly impacts survival and quality of life in advanced cancers.
- Denosumab (DMAB), a RANKL inhibitor, prevents skeletal-related events (SREs).
- The RANK/RANKL axis is increasingly relevant with the rise of immune checkpoint inhibitors (ICIs).
Purpose of the Study:
- To investigate potential synergistic antitumor effects of combining immunotherapy with denosumab.
- To explore the impact of sequential administration of ICIs and denosumab on patient outcomes.
Main Methods:
- Retrospective analysis of the IMMUCARE database (patients receiving ICI since 2014 with bone metastases).
- Stratification into groups: ICI alone, ICI then denosumab, denosumab then ICI.
- Evaluation of overall survival (OS), progression-free survival (PFS), and treatment line switches using survival curves and Cox regression.
Main Results:
- No significant OS or PFS difference between ICI monotherapy and combined ICI-denosumab overall.
- Patients receiving denosumab *after* ICI initiation showed a significant advantage (p=0.022) compared to no denosumab or denosumab before ICI.
- 114 of 268 patients received ICI with denosumab; 17 received denosumab after ICI initiation.
Conclusions:
- Sequential administration of ICI followed by denosumab may offer potential benefits in managing bone metastases.
- While not statistically significant overall, the sequential approach warrants further investigation.
- Prospective trials focusing on first-line immunotherapy are recommended to clarify this therapeutic strategy.
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