Key clinical point: This meta-analysis suggests that the use of androgen receptor inhibitors (ARIs; enzalutamide, apalutamide, or darolutamide) is associated with an increased risk of fall and fracture in patients with prostate cancer.

Major finding: In the pooled analysis, use of ARI was associated with a higher risk of all-grade falls (relative risk [RR], 1.80; P less than .001), grade 3 or greater fall (RR, 1.60; P less than .001), all-grade fractures (RR, 1.59; P less than .001), and likely grade 3 or greater fracture (RR, 1.71; P = .01).

Study details: A meta-analysis of 11 randomized clinical trials including 11,382 men with a median age of 72 years (6,536 men were in the ARI group and 4,846 men were in the control group).

Disclosures: No study sponsor was identified. Dr. J. M. Kolesar reported receiving ownership interest from Helix Diagnostics outside the submitted work. No other disclosures were reported.

Commentary

“Androgen receptor inhibition (ARI) is widely utilized in men with advanced prostate cancer. Previous studies have suggested that ARI may be associated with a higher incidence of falls and fractures in some patients with prostate cancer. As nearly all men treated with ARI will have concomitant androgen deprivation therapy (and potential associated osteopenia), falls are of great concern. In this meta-analysis, 11 studies were analyzed and the incidence of falls and fractures, respectively, was compared between an ARI group (enzalutamide, darolutamide, or apalutamide) and a control group (abiraterone, bicalutamide, or placebo). The incidence of falls and fractures was higher in the group receiving ARI (relative risk 1.8, 1.59, respectively). The reasons for this association are unclear but could include medication effects on the central nervous system, sarcopenia, fatigue, or other medications. This meta-analysis suggests that attention should be paid to falls-risk screening and appropriate use of bone-targeting agents.”

Mark Klein, MD