Toremifene decreases vertebral fractures in men younger than 80 years receiving androgen deprivation therapy for prostate cancer

Abstract

Purpose: Androgen deprivation therapy is associated with an increased fracture risk. In a recent phase III trial toremifene significantly decreased vertebral fractures in men on androgen deprivation therapy. Similar to other selective estrogen receptor modulators, toremifene was associated with an increase in venous thromboembolic events with the greatest risk in men 80 years old or older. In this post hoc analysis we evaluated the efficacy and safety of toremifene in men younger than 80 years.

Materials and methods: This analysis included 847 men younger than 80 years, of whom 430 received toremifene 80 mg by mouth daily and 417 received placebo for up to 24 months. The primary end point was new vertebral fractures. Secondary end points included fragility fractures, bone mineral density and safety.

Results: Compared with placebo, toremifene decreased the relative risk of new vertebral fractures by 79.5% (95% CI 29.8-94.0, p <0.005). The new vertebral fracture incidence was 1.0% for toremifene and 4.8% for placebo (absolute risk reduction 3.8%). Compared with placebo, toremifene significantly decreased the incidence of nontraumatic fracture or greater than 7% bone loss by 24 months (p <0.0001). Toremifene also significantly increased bone mineral density at all measured sites (all comparisons p <0.001). The incidence of venous thromboembolic events was similar in the toremifene and placebo groups (2.1% and 1.0%, respectively, p = 0.26). The rates of other adverse events were also similar between the groups.

Conclusions: Toremifene significantly decreased new vertebral fractures in men younger than 80 years receiving androgen deprivation therapy for prostate cancer. The risk of venous thromboembolic events was lower than in the overall study population, suggesting an improved risk-benefit profile in younger men.

Figure 1

Percentage change from baseline in BMD at month 24 (MITT population). The LS mean (SE) differences between the toremifene and placebo groups are shown for each site. BMD=bone mineral density; LS=least squares; MITT=modified intent-to-treat. ^aP<0.001 vs placebo. ^bMean (SD) change from baseline to month 24: toremifene, 0.01 (0.04); placebo, −0.02 (0.06). ^cMean (SD) change from baseline to month 24: toremifene, 0.00 (0.03); placebo, −0.02 (0.03). ^dMean (SD) change from baseline to month 24: toremifene, 0.00 (0.03); placebo, −0.02 (0.04).

Figure 2

Percentage change from baseline in bone turnover markers at month 24 (MITT population). The LS mean (SE) differences between the toremifene and placebo groups are shown for each marker. BSAP=bone-specific alkaline phosphatase; CTX=C-telopeptide; LS=least squares; MITT=modified intent-to-treat. ^aP<0.001 vs placebo. ^bP=0.01 vs placebo.