Comparative Treatment Persistence with Bone-Targeting Agents Among Asian Patients with Bone Metastases from Solid Tumors: A Multinational Retrospective Cohort Study

Background: The efficacy of bone-targeting agents has been confirmed, but the generalizability of results to Asia is in question. Objective: We aimed to evaluate and compare treatment persistence and re-initiation with different bone-targeting agents among patients with bone metastases from solid tumors. Methods: This population-based cohort study included patients with bone metastasis with breast, lung, or prostate cancer who initiated bone-targeting agents, including denosumab, zoledronic acid, and pamidronate in Taiwan (2013–17), Hong Kong (2013–17), and Korea (2012–16). We described the patients’ persistence with bone-targeting agents, by evaluating the interruption probability, and compared risks of treatment interruption. The rates of re-initiation with index bone-targeting agents were evaluated. Results: We included 5127 patients (denosumab: 3440, zoledronic acid: 1210, pamidronate: 477) from Taiwan, 883 patients (denosumab: 458, zoledronic acid: 357, pamidronate: 68) from Hong Kong, and 4800 patients (zoledronic acid: 4068, pamidronate: 732) from Korea. Compared with zoledronic acid, denosumab had a lower risk of interruption in Taiwan (adjusted hazard ratio: 0.44; 95% confidence interval 0.40–0.48) and Hong Kong (0.36; 0.28–0.45). However, pamidronate was more likely to be interrupted than zoledronic acid in Taiwan (1.31; 1.11–1.54) and Korea (2.06; 1.83–2.32), but not in Hong Kong (1.13; 0.71–1.78). After discontinuation, original treatments with denosumab in Taiwan and zoledronic acid in Hong Kong were more likely to be resumed, while in Korea, the rates were similar among the bisphosphonates. Conclusions: Denosumab was associated with a lower risk of interruption than bisphosphonates in patients with bone metastases in Taiwan and Hong Kong. Further investigations may be required to verify patients’ actual reasons for discontinuation.