Use of bone modifying agents for metastatic castrate-resistant prostate cancer.

Abstract

55 Background: Bone modifying agents (BMAs) prevent skeletal related events (SREs) among patients with metastatic, castrate-resistant prostate cancer (mCRPC) involving the bone. The utilization of BMAs among patients with mCRPC and bone metastasis has not been well defined, and the number of patients who may benefit but are undertreated is not known. We conducted this study to measure patterns of BMA among mCRPC patients. Methods: We used linked SEER cancer registry and Medicare claims data. Our cohort included men newly diagnosed with de-novo stage IV prostate adenocarcinoma during 2007-2015, with followup through 2016. We included those age > = 66 at diagnosis, had continuous enrollment in Medicare Parts A and B from 180 days prior to diagnosis through the outcome period and Part D from diagnosis through outcome period, and who received androgen deprivation therapy. We further limited the cohort to those who subsequently received a CRPC-defining therapy (eg., abiraterone, sipuleucel-T, docetaxel if occurring prior to CHAARTED trial results). We grouped the cohort according to those who did vs. did not have evidence of bone metastasis in claims. Our primary outcome was receipt of a BMA (zoledronic acid or denosumab) within 180 days of initiating a CRPC-defining therapy. Among patients who received BMAs after initiating CRPC therapy, we further characterized the time at which they first initiated a BMA. Results: Our sample included 1,303 patients, of which 85% had evidence of bone metastasis. Overall, 58% received a BMA within 180 days of initiating a CRPC-defining therapy. 66% of patients with evidence of bone metastasis received BMAs, compared to 16% of those without evidence. Of patients who received BMAs, 38% first received BMAs between 90 days prior to starting CRPC therapy and 180 days after; the remaining 62% were previously receiving BMAs during the castrate-sensitive phase of disease. Among patients with evidence of bone metastasis who initiated CRPC-defining therapy in 2007-2009, 65% received BMAs; this proportion was 69% and 64% for those began CRPC therapy during 2010-2013 and 2014-2016, respectively. Conclusions: Approximately two-thirds of patients with mCRPC and bone metastases received BMAs within 180 days of initiating a CRPC-defining therapy. In most cases BMA therapy was initiated while patients still had castrate-sensitive disease, for which BMAs are indicated only at lower doses for the prevention of osteoporotic fractures. Further work is needed to understand whether real-world dosing is in line with clinical indications, and whether the one-third of patients who did not receive BMA therapy appropriately reflects the proportion of patients with contraindications. Further work is also needed to characterize patient and provider factors associated with appropriate BMA use.