Androgen receptor inhibitors linked to increased fall and fracture risk in prostate cancer patients

The use of androgen receptor inhibitors (ARIs) in patients with prostate cancer was associated with an increased risk of fall and fracture, according to a systematic review and meta-analysis of 11 randomized clinical trials.¹

The analysis, which was published in JAMA Network Open, showed that among patients receiving the ARIs enzalutamide (Xtandi), apalutamide (Erleada), or darolutamide (Nubeqa), there was a 1.8 times higher risk of fall compared with the risk in patients receiving one of the control treatments (placebo, bicalutamide, or abiraterone acetate [Zytiga]). The risk of fracture was 1.6 times higher with ARIs versus control.

Despite their findings, the study authors recommended continued use of these agents in the appropriate patients.

“Although the incidence of fall/fracture was noted to be a higher risk in patients receiving ARIs, it is still a rare adverse event. 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,” first study author Zin W. Myint, MD, Division of Medical Oncology, Department of Internal Medicine, University of Kentucky, Markey Cancer Center, Lexington, and coauthor wrote in their paper.

“Oncologists should consider incorporating the fall-risk screening tool in older, active, patients with cancer in clinics. Appropriate use of bone-targeted agents should be considered in those patients as per established guidelines,” added Myint, et al.

The 11 studies used for the analysis came from the Cochrane, Scopus, and MedlinePlus databases. Overall, the analysis included data from 11,382 men, comprising 6536 in the ARI group and 4846 in the control group. The median age was 72 years (range, 43-97). Disease histology included nonmetastatic castration-resistant prostate cancer, metastatic hormone-sensitive prostate cancer, and metastatic castration-resistant prostate cancer. Of the 11 studies, 8 used enzalutamide, 2 used apalutamide, and 1 used darolutamide. The median duration of therapy was 15 months (range, 5.4-20.5) versus 8 months (range, 5.4-18.3) in the ARI versus control groups, respectively.

In the ARI group, falls were reported for 525 patients (8%) compared with 221 patients (5%) in the control group. There were 242 (4%) versus 107 (2%) fractures in the 2 groups, respectively.

The relative risk of all-grade falls was 1.8 times higher (P <.001) in the ARI group and the relative risk of grade ≥3 falls was 1.6 times higher (P <.001). Also for the ARI group, the relative risk of all-grade fracture was 1.59 times higher (P <.001) and the relative risk of a likely grade ≥3 fracture was 1.71 times higher (P = .01).

“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,” Myint et al wrote in their conclusion.

References

1. Myint ZW, Momo HD, Otto DE, et al. Evaluation of fall and fracture risk among men with prostate cancer treated with androgen receptor inhibitors: a systematic review and meta-analysis. JAMA Netw Open. 2020;3(11):e2025826. doi: 10.1001/jamanetworkopen.2020.25826