Clinical efficacy and safety of long-term treatment, discontinuation, and extended dosing intervals of denosumab treatment for solid cancer bone metastasis: A retrospective study.

Background: Metastatic bone tumors in solid cancer often induce excessive local bone resorption leading to skeletal related events (SRE) which may impact patients' quality of life and survival of the primary cancer. Denosumab, a bone resorption inhibitor, is commonly used to prevent SRE in patients with solid cancer bone metastasis. However, as cancer treatment advances, patients with long-term treatment, discontinuation, and extended dosing intervals of denosumab are seen in real-world clinical practice, and questions arise regarding the efficacy and safety of such cases.

Methods: We retrospective evaluated a total of 298 patients with bone metastasis of solid cancer who received denosumab treatment between 2012 and 2022. We evaluated the rates of SRE and adverse events from the medical records. To evaluate the impact of extended dosing intervals, patients were divided to short and long interval groups consisting of patients with mean dosing interval of shorter and longer than six weeks, respectively.

Results: Patients with lung and other cancers, patients with prior SRE, and patients with lung metastasis showed higher risks of SRE. Osteonecrosis of the jaw (ONJ) was seen in 11.1 % of the cases and the highest incidence rate of ONJ was seen in the third year of treatment. Atypical femoral fracture was seen in one case with a dosing period of 217 weeks. Discontinuation of denosumab led to an increase of SRE, 25 weeks after the final administration. Extended dosing intervals of denosumab did not increase the SRE risk, however, did not reduce the risk of adverse events either.

Conclusion: Severe adverse events should be noted in long-term treatment cases. Denosumab holiday is suggested to be limited to less than six months to mitigate SRE risk. Extending dosing intervals beyond the standard regimen did not increase the risk of SRE nor decrease the risk of adverse events.