New study from the Royal Marsden (Chris Parker) [1].
"This was a prospective, multicenter phase II study of radium-223 in 36 men with mCRPC and a reference cohort (n = 36) matched for fracture risk and not treated with radium-223."
"Thirty-six patients were treated with up to six 4-week cycles of radium-223.
"With a median follow-up of 16.3 months, 74 new fractures were identified in 20 patients. Freedom from fracture was 56% ... at 12 months.
"... prior corticosteroid use was associated with risk of fracture.
"In the reference cohort (n = 36), 16 new fractures were identified in 12 patients over a median follow-up of 24 months.
"Across both cohorts, 67% of all fractures occurred at uninvolved bone."
"Men with mCRPC, and particularly those treated with radium-223, are at risk of fracture. They should receive a bone health agent to reduce the risk of fragility fractures."
***
Below is a video interview with Chris Parker 3 years ago: [2]. Will give some background on Radium-223.
***
In the interview, Dr. Parker describes the combination of Abiraterone & Radium-223 as a natural, since both are well tolerated and work in different ways. However. concurrent use was subsequently associated with greater risk of bone fracture.
Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial [3]
"Between March 30, 2014, and Aug 12, 2016, 806 patients were randomly assigned to receive radium-223 (n=401) or placebo (n=405) in addition to abiraterone acetate plus prednisone or prednisolone. The study was unblinded prematurely, on Nov 17, 2017, after more fractures and deaths were noted in the radium-223 group than in the placebo group (in an unplanned ad-hoc analysis), but all patients had completed radium-223 or placebo before this date."
"The addition of radium-223 to abiraterone acetate plus prednisone or prednisolone did not improve symptomatic skeletal event-free survival in patients with castration-resistant prostate cancer and bone metastases, and was associated with an increased frequency of bone fractures compared with placebo. Thus, we do not recommend use of this combination."
-Patrick
Notes.
mCRPC = metastatic castration-resistant prostate cancer
Radium-223 = Xofigo (previously Alpharadin)
[1] pubmed.ncbi.nlm.nih.gov/339...
Clin Genitourin Cancer
. 2021 Apr 4;S1558-7673(21)00083-5. doi: 10.1016/j.clgc.2021.03.020. Online ahead of print.
Fracture Risk in Men with Metastatic Prostate Cancer Treated With Radium-223
Adham Hijab 1 , Sebastian Curcean 1 , Nina Tunariu 2 , Holly Tovey 3 , Roberto Alonzi 4 , John Staffurth 5 , Matthew Blackledge 3 , Anwar Padhani 6 , Alison Tree 1 , Helen Stidwill 1 , Jessica Finch 4 , Peter Chatfield 3 , Sophie Perry 3 , Dow Mu Koh 2 , Emma Hall 3 , Chris Parker 7
Affiliations collapse
Affiliations
1 The Royal Marsden NHS Foundation Trust, London, UK.
2 The Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK.
3 The Institute of Cancer Research, London, UK.
4 Mount Vernon Cancer Centre, Northwood, UK.
5 Velindre Cancer Centre, Cardiff, UK.
6 Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, Northwood, UK.
7 The Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK. Electronic address: chris.parker@icr.ac.uk.
PMID: 33958296 DOI: 10.1016/j.clgc.2021.03.020
Abstract
Background: Radium-223 is a bone-seeking, alpha-emitting radionuclide used in metastatic castration-resistant prostate cancer (mCRPC). Radium-223 increases the risk of fracture when used in combination with abiraterone and prednisolone. The risk of fracture in men receiving radium-223 monotherapy is unclear.
Patients and methods: This was a prospective, multicenter phase II study of radium-223 in 36 men with mCRPC and a reference cohort (n = 36) matched for fracture risk and not treated with radium-223. Bone fractures were assessed using whole-body magnetic resonance imaging. The primary outcome was risk of new fractures.
Results: Thirty-six patients were treated with up to six 4-week cycles of radium-223. With a median follow-up of 16.3 months, 74 new fractures were identified in 20 patients. Freedom from fracture was 56% (95% confidence interval, 35.3-71.6) at 12 months. On multivariate analysis, prior corticosteroid use was associated with risk of fracture. In the reference cohort (n = 36), 16 new fractures were identified in 12 patients over a median follow-up of 24 months. Across both cohorts, 67% of all fractures occurred at uninvolved bone.
Conclusions: Men with mCRPC, and particularly those treated with radium-223, are at risk of fracture. They should receive a bone health agent to reduce the risk of fragility fractures.
Keywords: Bone health; Bone metastasis; Metastatic castration-resistant prostate cancer; Skeletal-related events.
Copyright © 2021. Published by Elsevier Inc.
***
***