Radium-223 & Fracture Risk

[pjoshea13]

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: [e-mail].

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.

***

[2] vimeo.com/251583163

***

[3] pubmed.ncbi.nlm.nih.gov/307...

[cesanon]

Nice to know.

[V10fanatic]

Thanks for the heads up.