Wednesday 15 February 2012

Prostate cancer and Denosumab - Cancer Treatment Options ...

Metastasis to the bone is a common feature of prostate cancers. When prostate cancers metastasize to the bone, they hijack the bone remodelling process in order to be incorporated into the newly developed bone tissue. Denosumab is a monoclonal antibody designed to target the RANK ligand, a protein produced by osteoblast cells in order to promote bone remodelling.

In this study, patients with non-metastatic castration resistant prostate cancer (CRPC) with PSA values of greater than 8.0 ng/mL and/or a PSA doubling time (PSADT) of less than 10.0 months, Denosumab resulted in a 15% reduction of bone metastasis and increased the bone metastasis free survival time (BMST) by 4.2 months (29.5 vs. 25.2 months for placebo).

In a subgroup of this study, patients with aggressive disease (PSADT of less than 6 months), treatment with Denosumab resulted in a significant (23%) reduction of bone metastasis with a BMST of 25.9 months compared to only 18.7 months for the placebo. See table 1.

I like this study because it stratified the patient population based on disease aggressiveness and identified a sub-group of patients most likely to benefit from Denosumab.

TABLE 1: Comparison of the effects of Denosumab in reducing bone metastasis in overall and aggressive disease subgroup.

Population Sample size BMFS median (months) BMFS treatment difference (months) Hazard ratio 95% Confidence interval P-value
All patients D: 716
P: 716
D: 29.5
P: 25.2
4.2 0.85 0.73 ? 0.98 0.028
PSADT <6 months D: 419
P: 427
D: 25.9
P: 18.7
7.2 0.77 0.64 ? 0.93 0.006

D=Denosumab; P=Placebo

Effect of Denosumab on Prolonging Bone-Metastasis-Free Survival (BMFS) in Men with Non-Metastatic Castrate-Resistant Prostate Cancer (CRPC) Presenting with Aggressive PSA Kinetics.

Source: http://www.ctoam.com/denosumab-reduces-bone-metastasis-in-aggressive-prostate-cancers/

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