Responder analysis of the effects of denosumab on bone mineral density in men receiving androgen deprivation therapy for prostate cancer

Abstract

Background: Denosumab, a fully human monoclonal antibody against RANK ligand, increased bone mineral density (BMD) and reduced fracture risk vs placebo in a phase 3 trial in men with prostate cancer on androgen deprivation therapy (ADT). The present analysis of this study evaluated BMD changes after 36 months in responder subgroups and in individual patients for three key skeletal sites (lumbar spine (LS), femoral neck (FN) and total hip (TH)) and the distal radius.

Methods: Men with nonmetastatic prostate cancer receiving ADT were treated with subcutaneous denosumab 60 mg (n=734) or placebo (n=734) every 6 months for up to 36 months in a phase 3, randomized, double-blind study. Patients were instructed to take supplemental calcium and vitamin D. For this BMD responder analysis, the primary outcome measure was the percentage change in BMD from baseline to month 36 at the LS, FN and TH as measured by dual-energy X-ray absorptiometry. BMD at the distal 1/3 radius at 36 months was measured in a substudy of 309 patients.

Results: At 36 months, significantly more patients in the denosumab arm had increases of >3% BMD from baseline at each site studied compared with placebo (LS, 78 vs 17%; FN, 48 vs 13%; TH, 48 vs 6%; distal 1/3 radius, 40 vs 7% (P<0.0001 for all)). BMD loss at the LS, FN and TH occurred in 1% of denosumab-treated patients vs 42% of placebo patients, and BMD gain at all three sites occurred in 69% of denosumab patients vs 8% of placebo patients. Lower baseline BMD was associated with higher-magnitude BMD responses to denosumab at the LS, FN and TH.

Conclusions: In men with prostate cancer receiving ADT, significantly higher BMD response rates were observed with denosumab vs placebo. Patients with lower baseline T-scores benefited the most from denosumab treatment.

Figure 1. Responder Analysis: BMD Percent Change from Baseline at 36 Months

* p < 0.0001 vs placebo n = number of patients evaluated

Figure 2

Waterfall Analysis: Individual Percent Changes in BMD from Baseline at 36 Months

Figure 2

Waterfall Analysis: Individual Percent Changes in BMD from Baseline at 36 Months

Figure 3

Figure 3a. Mean change in BMD response in the denosumab group at 36 mo *Within-group ANCOVA test for heterogeneity Figure 3b. Mean change in BMD response in the placebo group *Within-group ANCOVA test for heterogeneity

Figure 3

Figure 3a. Mean change in BMD response in the denosumab group at 36 mo *Within-group ANCOVA test for heterogeneity Figure 3b. Mean change in BMD response in the placebo group *Within-group ANCOVA test for heterogeneity