Bone targeted therapy and skeletal related events in the era of enzalutamide and abiraterone acetate for castration resistant prostate cancer with bone metastases

Background: In an era of multiple life-prolonging therapies for metastatic castration resistant prostate cancer (mCRPC), the optimal timing of initiation and duration of antiresorptive bone targeted therapy (BTT) to prevent skeletal related events (SREs) is unknown. Methods: To assess practice patterns of BTT use and its associations with clinical outcomes in a high-volume center in the modern era of metastatic CRPC management, a retrospective cohort of patients treated for mCRPC with BM between 2007 and 2017 was identified from a single institutions clinical research database. Study endpoints included time from the diagnosis of CRPC to the onset of SRE or OS. Cox proportional hazards model assessed association of BTT use with time to first SRE and OS. Results: In total, 249 patients were identified; median follow-up was 7.7 (95%CI: 5.7–10.2) years. On multivariable analysis, patients with 4 or more BM at diagnosis of mCRPC who received BTT with abiraterone acetate or enzalutamide as first line therapy had a 42% reduced risk of developing an SRE (HR 0.58; 95%CI: 0.36–0.95) compared to those who never received BTT or received it in second line. No such effect was observed in patients with 1–3 BM. No OS difference was noted in patients who received BTT, whether with first line therapy or without. This study is limited by retrospective nature at a single institution. Conclusions: Our hospital registry data indicate a potential benefit in terms of SRE prevention for early use of antiresorptive BTT in combination with life prolonging CRPC therapies for patients with CRPC and at least 4 BM.