Initiation and adherence with bone-targeting agents in US men with bone metastases from prostate cancer

Background: Bone metastases (BM) are common in advanced prostate cancer patients and can lead to serious skeletal-related events (eg, pathological fracture). Two bone-targeting agents (BTAs) are approved in the US for prevention of skeletal-related events in men with BM from prostate cancer – denosumab and zoledronic acid. We sought to provide a current and comprehensive description of BTA use in this population. Methods: Using structured and unstructured data (processed via technology-enabled abstraction) from a large, longitudinal electronic health record database of patients receiving care at oncology practices across the US (Flatiron Health), we identified adult prostate cancer patients with a confirmed diagnosis of BM in 2012/2013 and no evidence of BTA use in the 6 months prior to diagnosis. Patients were followed through 04/30/2015. We estimated the cumulative incidence of BTA initiation after BM diagnosis, treating death as a competing event. Among BTA users, we used multivariable repeated measures generalized linear models to examine demographic/clinical factors associated with non-adherence (defined as absence of treatment in a 30-day interval to closely reflect the labels). Results: Of 897 men in the cohort, mean age at BM was 71 years, 22% also had non-bone metastases, and 8% experienced a prior skeletal-related event. During 1150 person-months of follow-up, 706 patients initiated a BTA and 77 patients died prior to initiation. The cumulative incidence of BTA initiation after BM diagnosis was 24% (95% confidence interval [CI] 21-26%) at 30 days, 76% (95% CI 68-84%) at 180 days, and 89% (95% CI 74-100%) at 1 year. Adherence at 6, 12, and 24 months after initiation was 86% (95% CI 83-88%), 73% (95% CI 70-76%), and 32% (95% CI 28-35%), respectively. We observed an increased risk of non-adherence in men who initiated treatment shortly after a diagnosis of BM (treatment initiated < 3 vs. ≥ 3 months after BM diagnosis). Conclusions: This study of real-world treatment patterns in a population of prostate cancer patients with BM treated in oncology clinics in the US found that most men initiated a BTA > 30 days after BM diagnosis. Adherence to BTAs decreased over time, with a substantial decline after 12 months.