Routine use of denosumab for prevention of skeletal-related events in patients with bone metastases from prostate carcinoma in Bulgaria: a prospective observational study

Abstract

Bulgarian real-world data on denosumab use for the prevention of skeletal-related events (SREs) associated with bone metastases (BM) from prostate cancer (PC) are lacking. This observational study enrolled 100 adult PC patients with ≥1 BM receiving denosumab (EUPAS26983). Patients’ routine treatment was observed retrospectively for ≤6 months and prospectively for 12 months. Denosumab use and safety, SRE incidence, denosumab persistence (allowing ≤2 missed doses), and pain severity were evaluated using descriptive statistics. Denosumab was initiated at a median (Q1, Q3) of 1.8 (0.6, 9.6) months following BM diagnosis with earlier initiation in hormone-sensitive (HSPC; 1.5 [0.6; 4.2]; n = 74) than castration-resistant PC (CRPC; 7.9 [0.8; 16.4]; p = .082; n = 26) and in younger (<65 years; 1.2 [0.3; 2.8]; n = 19) than older patients (≥65 years; 2.0 [0.7; 9.6]; p = .161; n = 81). Ten SREs were recorded during the retrospective and 10 during the prospective period; none were symptomatic. Denosumab was used for a median of 472 (387, 599) days overall and for 443–464 days without missing more than two doses (persistence). The proportion of patients reporting acceptable pain (score ≤4 of 10) increased from 6% at baseline to 22% at month 12. Twenty-four denosumab-related adverse events were reported, 2 were serious (osteomyelitis, osteitis) and 5 were related to osteonecrosis of the jaw. In Bulgarian clinical practice, denosumab use was associated with the prevention of symptomatic SREs and pain improvement. Denosumab was mostly used persistently. No symptomatic SREs were reported. Safety findings were consistent with previous reports of denosumab use in PC.

Keywords:

• Prostate cancer
• bone metastases
• skeletal-related events
• denosumab
• persistence
• adherence

Acknowledgements

The authors would like to thank Margit Hemetsberger, PhD, of Hemetsberger Medical Services, Vienna, Austria, for medical writing support, funded by Amgen Bulgaria, EOOD. The authors would like to thank all the investigators and patients.

Authors’ contributions

V.I. and K.B. contributed substantially to the study design and concept. A.T. and M.P. were involved in data acquisition. A.O. conducted the data analyses. All authors assisted with interpretation of the data. All authors were involved in drafting of the manuscript, provided critical revisions for important intellectual content, approved the final version submitted for publication, and agreed to be accountable for all aspects of the work.

Disclosure statement

A.T. and M.P. were principal investigators of this study. V.I., K.B. are employees of Amgen and hold Amgen stocks. A.O. declares no conflict of interest.

Ethics

The Bulgarian centralized ethics committee for clinical trials provided the ethics approval of the study protocol and the Bulgarian drug agency provided the regulatory approval (registration number: EKKI/CT-0365, approval date: 08 May 2019).

The study was conducted in accordance with country-specific legal and regulatory requirements, as well as with scientific purpose, value, and rigor. It followed the generally accepted research practices described in GEP guidelines issued by the International Epidemiological Association (IEA). All data were handled in the strictest confidence in conformity with national and European data protection regulations (such as Directive 95/46/EC). Written informed consent was obtained from all individual participants included in the study.

Data availability statement

Qualified researchers may request data from Amgen clinical studies. Complete data are available at the following: https://wwwext.amgen.com/about/how-we-operate/policies-practices-and-disclosures/ethical-research/clinical-data-transparency-practices/clinical-trial-data-sharing-request.

Additional information

Funding

This study was funded by Amgen Bulgaria EOOD.