Optimizing antiresorptive treatment in patients with bone metastases: time to initiation, switching strategies, and treatment duration

PURPOSE: The aim of this study was to investigate the optimal use of antiresorptive therapy in patients with metastatic cancer in terms of time to treatment initiation, switching strategy in case of skeletal-related event (SRE) or skeletal disease progression, and treatment efficacy beyond 2 years. METHODS: We conducted a single-center retrospective cohort study including consecutive cancer patients with bone metastases that have received antiresorptive treatment between 2009 and 2015. The outcomes of interest were the time to first and subsequent symptomatic skeletal event (SSE), the skeletal morbidity rate, and the incidence of antiresorptive therapy-specific adverse events depending on the research question. RESULTS: In total, 255 patients included in our study cohort. The time to treatment initiation (direct (n = 143 patients) vs. delayed (n = 87 patients) defined as > 3 months after diagnosis of bone metastases) was not found to influence the time to SSE in (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.65–1.34) with comparable toxicity. Switching strategy after first SRE or due to skeletal disease progression from bisphosphonates to denosumab was independently associated with longer time to SRE (HR 0.47, 95% CI 0.25–0.88, p value = 0.019) compared with continuation with the same bisphosphonate. Using the landmark approach at 24 months and including 121 patients that survived for more than 2 years, we found that treatment continuation beyond 2 years was associated with longer time to first SSE after 2 years (HR 0.41; 95% CI 0.19–0.93). CONCLUSIONS: Our hypothesis-generating results support a more individualized approach on antiresorptive treatment including the lack of detrimental effect when the treatment is delayed, the potential benefit of switching strategy after skeletal disease progression or SSE, and the benefit of continuing antiresorptive treatment beyond 2 years.