With all the caveats of an observational study, even if the publisher is highly regarded...
A study in JBMR plus found that bone-modifying agents like bisphosphonates and denosumab are linked to improved overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC).
The study analyzed 420 mCRPC patients, with 60% receiving bone-modifying agents.
While no significant differences in progression-free survival were observed, patients who received bone-modifying agents had a significantly longer overall survival (58 months vs. 45 months).
Within the group receiving bone-modifying agents, no significant differences in survival were seen between those on bisphosphonates versus denosumab. The rate of osteonecrosis of the jaw was 12% in both groups. The study suggests that despite low administration rates, these agents offer a meaningful survival benefit in mCRPC patients with bone metastases.
You are correct that while bone-modifying agents (BMAs), such as zoledronic acid and denosumab, effectively reduce skeletal-related events (SREs) in metastatic prostate cancer, they have not consistently demonstrated an improvement in overall survival (OS) in most clinical trials. Their primary role is to manage bone health and complications, not to directly prolong survival.
Key Clinical Trials:
1. Zoledronic Acid
Trial: Phase III Trial by Saad et al. (NEJM, 2002)
Population: Men with castration-resistant prostate cancer (CRPC) and bone metastases.
Findings:
Zoledronic acid significantly reduced SREs compared to placebo.
No statistically significant improvement in overall survival.
Conclusion: Effective for reducing SREs, but not for extending OS.
2. Denosumab
Trial: 147 Study (Lancet, 2011)
Population: CRPC with bone metastases.
Findings:
Denosumab delayed the time to first SRE compared to zoledronic acid (20.7 months vs. 17.1 months).
No difference in OS or disease progression.
Conclusion: Superior to zoledronic acid in preventing SREs, but no OS benefit.
3. STAMPEDE Trial (2022)
Population: Hormone-sensitive prostate cancer (HSPC) with high-risk features.
Findings:
Adding zoledronic acid to systemic therapy (with or without docetaxel) did not improve overall survival.
Conclusion: BMAs in this setting are not for survival benefit but may reduce bone complications.
Summary:
BMAs like zoledronic acid and denosumab:
Primary Role: Prevent skeletal complications in metastatic prostate cancer.
Impact on Survival: Clinical trials have not shown a statistically significant improvement in overall survival for either drug in prostate cancer.
Their use remains essential for supportive care in patients with bone metastases, alongside systemic treatments like ADT, chemotherapy, and AR-directed therapies.
Findings: Denosumab was more effective than zoledronic acid in delaying skeletal-related events in men with bone metastases from castration-resistant prostate cancer.
I believe that it is a good idea to start with a yearly zoledronic acid infusions in order to see if you could tolerate it. If you can tolerate the zoledronic acid infusions than switch to prolia six monthly denosumab injections an you could continue up to 10 years. After that 10 years you could (should) switch back to zoledronic acid infusions and then stop if you want to stop because stopping denosumab is risky.
It sounds like you're considering a treatment plan involving bone health management, likely in response to either a diagnosis related to prostate cancer or associated treatment. Zoledronic acid (a bisphosphonate) and denosumab (Prolia, a monoclonal antibody) are both commonly used to strengthen bones, particularly in conditions like osteoporosis or bone metastasis from cancers.
Starting with yearly zoledronic acid infusions to see if you tolerate them is a reasonable approach. If you can tolerate the zoledronic acid, switching to Prolia for six-monthly injections can be considered. Prolia is often used for longer-term bone health but has a notable risk of complications if stopped abruptly, such as a rebound effect leading to bone fractures. Hence, after 10 years of Prolia use, transitioning back to zoledronic acid may be prudent, especially if you're at risk for long-term bone issues.
Before proceeding, it's always best to discuss this strategy with your healthcare provider to evaluate your specific bone health and any potential risks based on your individual situation.
We cant draw any conclusions from Chat Gpt which first of all uses conventional sources (not TA's newsletters) and secondly doesnt address the two questions presented above. 1/ do either BM vs placebo further overall survival, progressive free survival, mets free survival , and radiographic evidenced progression? 2/ and the already significant data of the diff bet biophophates and denosumabs re adverse jaw side effects. Ive seen repeatedly 3-4% difference.
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