SIU 2017: Bone Targeted Treatment in Advanced Prostate Cancer

Lisbon, Portugal ( Dr. Saad focused his talked on bone targeted therapy in advanced prostate cancer. While the number of treatment options continues to grow, we must not forget about the potential implications of these treatments. Many of them will significantly affect bone health, which can have lasting impact on patients, leading to significant complications, including death.

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:

  1. Reduced SREs
  2. Longer time to first SRE
  3. Likely improved overall survival (studies hint at this)
At this time, it is only indicated for metastatic CRPC. There is no indication for metastatic hormone-sensitive PCa.

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
             - Alkaline phosphatase decline is a reliable marker of improved response
             - 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

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