Androgen receptor inhibitors implicated in fall, fracture risk in prostate cancer
medwireNews: Treatment with androgen receptor inhibitors (ARIs) is associated with an increased risk for falls and fractures in men with prostate cancer, show findings from a meta-analysis.
The investigators note, however, that falls and fractures were “still a rare adverse event,” and they add: “Considering the severity of the disease and that ARIs have shown significant improvement in overall survival, the benefits may outweigh the risk of fall and fracture in some individuals.”
Zin Myint (University of Kentucky, Lexington, USA) and fellow researchers analyzed data from 11 randomized clinical trials including a total of 11,382 patients with nonmetastatic or metastatic castration-resistant prostate cancer or metastatic hormone-sensitive disease.
Patients were grouped according to ever having received ARIs (n=6536), namely enzalutamide, apalutamide, or darolutamide with androgen deprivation therapy (ADT) or other combinations, or not (n=4846); treatments in the control group included ADT, bicalutamide, abiraterone, and placebo.
Falls of any grade occurred in 8.0% of patients in the ARI group and 5.0% of those in the control group, while falls of at least grade 3 were reported in 1.0% and 0.6% of patients, respectively. This equated to a significant 80% increased risk for all-grade falls with ARIs versus other treatments, while the risk for grade 3 or worse falls was a significant 60% higher.
Similarly, ARIs were associated with a higher incidence of all-grade (4.0 vs 2.0%) and grade 3 or more severe (1.0 vs 0.5%) fractures than the control treatments, translating into a significant 59% and 71% increased risk, respectively, with receipt of ARIs.
The rates of all-grade falls and fractures differed by ARI type, with the highest incidence seen with apalutamide, at 12.0% and 10.0%, respectively, followed by enzalutamide (8.0 and 1.8%, respectively) and darolutamide (4.2 and 4.2%, respectively).
Myint et al say that “[t]o date, it is unclear why the ARI drug class is associated with higher risk of fall,” but they speculate that one possible reason could be the ability of ARIs to cross the blood–brain barrier.
“Another possible explanation is that the sarcopenia associated with ARIs has a higher risk for fall,” hypothesizes the team.
The researchers conclude in JAMA Network Open: “Further prospective studies are warranted to identify potential mechanisms and to develop strategies that include a fall risk assessment tool to examine the risk factors for falls or fracture.”
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