Bone metastases can cause pathologic fracture and spinal cord compression, and treatment may involve invasive surgery or radiotherapy. Skeletal-related events (SREs) encompass all the above, and almost all patients will have at least one SRE prior to death. These SREs will continue to occur with the new therapies.
Interestingly, more recent data also suggests that prostate metastases can yield new metastases – hence bone metastases control and bone microenvironment understanding is important moving forward. All the current therapies have a direct or indirect effect on the bone microenvironment.
Bone targeting therapies have demonstrated the following:
- Reduced SREs
- Longer time to first SRE
- Likely improved overall survival (studies hint at this)
Recent studies have demonstrated denosumab is clearly superior to zoledronic acid in an RCT – 18% risk reduction in time to first SRE.
Burden of Disease
He addressed a Canadian study that looked at the financial burden of SREs and treatment. Median survival of 2 years from SRE to death. 70% of patients had at least one symptomatic event before dying. Event rate was 50% in patients on bone targeted therapy. Cost of SREs is 3-fold in men with SRE compared to no SRE.
- Radium-223 (ALSYMPCA) trial
- Reviewed the key findings from this trial
- QOL improved on Radiam-223
- Time to first SRE was extended
- Patients that receive 5-6 injection vs. 1-4 infusions (or placebo) have significant OS benefit
- Asymptomatic patients at baseline did better than patients symptomatic at baseline
- ECOG 2 patients did much worse than ECOG 0-1 patients
Combination with Abi/Enza or Denosumab improved OS than monotherapy alone
Dr. Saad did note that older bone targeted therapies did demonstrate benefit in combination with other systemic therapies in an earlier PCa space – perhaps there is a role for Radium-223 in an earlier space as well, in conjunction with established therapies?
Randomized prospective studies combining with abiraterone and enzalutamide in hormone sensitive space – one study already completed (results pending) and one still ongoing.
Presented by: Fred Saad
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 37th Congress of Société Internationale d’Urologie - October 19-22, 2017- Lisbon, Portugal