authors: fizazi k et al, asco 2010 abstract: lba4507 reviewed by: dr. lori wood
DESCRIPTION
A randomized phase III trial of denosumab versus zoledronic acid in patients with bone metastases from castration-resistant prostate cancer (CRPC). Authors: Fizazi K et al, ASCO 2010 Abstract: LBA4507 Reviewed by: Dr. Lori Wood Date posted: Jun 18 2010. - PowerPoint PPT PresentationTRANSCRIPT
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A randomized phase III trial of denosumab versus zoledronic acid in patients with bone metastases from castration-resistant prostate cancer (CRPC)
Authors: Fizazi K et al, ASCO 2010Abstract: LBA4507Reviewed by: Dr. Lori WoodDate posted: Jun 18 2010
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Thank you for downloading this update. Please feel free to use it for educational purposes.
Please acknowledge OncologyEducation.ca and Dr. Wood when using these slides.
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STUDY RATIONALE
• Bone metastases very common in Prostate Cancer• RANK Ligand (RANKL) is a central mediator of bone
destruction• RANKL is overexpressed in PCa and stimulates the
maturation and activation of osteoclasts• Denosumab is a monoclonal antibody to RANKL• To date, i.v. Zoledronic Acid is the only drug shown to
decrease SRE in CRPC• Safety profile of Denosumab shown to be good
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R
Treatment A: Denosumab 120 mg sc q4wksPlaceboN=950
Treatment B: Zoledronic Acid 4 mg i.v. q4wksPlaceboN=951
STUDY DESIGN
- CRPCa- Metastases to bone- Also given Vit D/calcium- Statistics: - designed with non- inferiority and superiority- Primary outcome: - time to first SRE
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RESULTS
ZA DENO HR P value
Time To First SRE 17.1m 20.7m 0.82p=0.0002 (Non-Inferiority)
p=0.008 (Superiority)
SRE 41% 36%
Toxicity:• Acute Phase Rxn• Renal• ONJ
• Hypocalcemia
17.8%
16.2%
1.3% (n=12)
5.8%
8.4%
14.7%
2.3% (n=22)
12.8%
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STUDY COMMENTARY
• Denosumab increased time to first SRE compared to Zoedronic Acid (20.7m vs. 17.1m) thus, meeting the primary endpoint of the study
• Originally felt very little renal toxicity but 14.7% compared to 16.2%. This will have to be further defined.
• Incidence of ONJ is not less (2.3% vs. 1.3%)
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BOTTOM-LINE FOR CANADIAN MEDICAL ONCOLOGISTS
• There is now another class of drugs that affect SRE in CRPC– Denosumab: a monoclonal antibody to RANKL
• The time to first SRE is longer with Denosumab compared to Zoledronic Acid– But will need further details on the number and types of SREs
• Unfortunately, it still does have toxicity including renal and ONJ• We still do not have good predictors of who benefits the most from
bone targeted agents (for example: urine bone turnover markers) and when patients should be started/continued/stopped– Hopefully this will come with more research
• Hard to know at this point how much Canadian practice will change based on this study