Falls rank among the top causes of death and injuries among the elderly, and the risk increases significantly in older people being treated for cancer. Now, investigators are reporting that a newer class of drugs for advanced prostate cancer is associated with a significant increase in fall risk.
Called androgen receptor inhibitors, or ARIs, these drugs target testosterone, a hormone that accelerates the growth of prostate tumors. Unlike traditional hormonal treatments that interfere with the body’s ability to make testosterone (known as androgen deprivation therapy, or ADT), ARIs work by preventing testosterone from binding to its receptor on cancer cells. Three ARIs were evaluated in the study — apalutamide, enzalutamide, and darolutamide — and each can limit prostate cancer progression and extend survival. The investigators emphasized that the benefits of using ARIs outweigh the risk of falls and fractures, which are rare even in treated patients.
What the investigators did
To generate the findings, the investigators performed a systematic review of previously published studies comparing ARI treatments with placebo. In all, 11 studies enrolling a combined total of 11,382 men met the criteria for evaluation. The average age of the men was 72, and the ARI treatments lasted between 5.4 and 20.5 months. Men were excluded if they had a prior history of heart disease or seizure disorders.
What they found
Results showed that 525 of 6,536 ARI-treated men (8%) had suffered falls, compared to 221 of 4,846 men (5%) who were given a placebo. Roughly half the falls in both groups resulted in fractures. However, grade-3 fractures causing more severe injuries occurred 1.6 times more frequently in the men taking ARIs. Apalutamide was associated with the highest fall risk (12%), followed by enzalutamide at 8% and darolutamide at 4.2%.
Just why ARIs boost fall risk isn’t known. Apalutamide