A 24-month subgroup analysis of the effect of denosumab on bone mineral density in women with breast cancer undergoing aromatase inhibitor therapy.

Abstract

Abstract Abstract #2106 Background: Accelerated bone loss and fracture risk are expected consequences of adjuvant aromatase inhibitor (AI) therapy. We previously showed that denosumab, a fully human monoclonal antibody that inhibits RANK ligand (RANKL), significantly increased bone mineral density (BMD) at the lumbar spine and at all measured skeletal sites at 12 months compared with placebo in women with breast cancer undergoing adjuvant AI therapy (Ellis et al, 2007 SABCS). In this analysis, we assessed covariates that may influence treatment effects on BMD at the lumbar spine, total hip, femoral neck, and 1/3 radius at 24 months.
 Methods: Adult patients (pts) with hormone receptor-positive breast cancer, who had evidence of low bone mass and were receiving adjuvant AI therapy, were enrolled in this randomized, double-blind, placebo-controlled, phase 3 study. Pts were stratified according to length of previous AI therapy (≤ 6 vs > 6 months) and randomly assigned to receive, together with calcium and vitamin D, placebo (n=125) or denosumab 60 mg (n=127) subcutaneously every 6 months for 4 doses. Subgroup analysis was conducted using analysis of covariance and adjusted for treatment, stratification factor, baseline BMD value, densitometer type, and baseline BMD value-by-densitometer-type interaction.
 Results: At 24 months, greater increases in BMD were seen at all measured skeletal sites (both trabecular and cortical bone) for denosumab compared with placebo, regardless of the subgroup (table). Adverse events (AEs) occurred at a similar rate in both groups (91% denosumab, 90% placebo).
 Conclusion: In pts with breast cancer undergoing adjuvant AI therapy, twice-yearly denosumab treatment showed consistent increases in BMD across the skeleton at 24 months compared with placebo, regardless of subgroups.
 
 Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2106.