Denosumab (Xgeva), the recently approved and only therapy that prolongs bone metastasis-free survival in men with non-metastatic castrate-resistant prostate cancer (CRPC) who are at high risk for the spread of prostate cancer metastasis to bone seems to work best in men with very rapid prostate specific antigen (PSA) kinetics.

The large 1,432 man, placebo controlled, international phase III trial called the 147 Trial established denosumab as the only therapy to prolong bone metastasis-free survival (BMFS) in men with CRPC. Additional analyses of the data from the trial now shows that the benefits of denosumab is greatest in men who have at least a PSA value of at least 8.0 ng/mL or on a PSA doubling time of 10 months or fewer.

Specifically, among the entire study population, a monthly shot of denosumab prolonged BMFS by 4.2 months compared with placebo (hazard ratio

[HR]: 0.85; p = 0.028).

By looking at the data in subgroups according to PSA kinetics it was found that there were increasing denosumab benefits in conjunction with shorter PSA doubling time. As PSA doubling time decreased from 10 to 6 to 4 or fewer months, denosumab produced increasing delays in BMFS of 6.0 (HR: 0.84; p = 0.042), 7.2 (HR: 0.77; p = 0.006), and 7.5 months (HR: 0.71; p = 0.004), respectively.

From Abstract 6 – The ASCO Genitourinary Cancers Symposium, 2012

Joel T Nowak, M.A., M.S.W.