In a systematic review and meta-analysis reported in JAMA Network Open, Myint et al found that androgen receptor inhibitor therapy for prostate cancer was associated with an increased risk of both falls and fractures.
Study Details
The meta-analysis included 11 randomized trials reported through August 2019 comparing androgen receptor inhibitor therapy with placebo; the total population was 11,382 men, including 6,536 in the androgen receptor inhibitor group and 4,846 in the control group. Patients with such comorbidities as myocardial infarction, congestive heart failure, ventricular arrhythmia, unstable angina, heart block, bradycardia, uncontrolled hypertension, and seizure disorders were excluded from all studies.
Androgen receptor inhibitors were defined as enzalutamide, apalutamide, or darolutamide alone or in combination, including in combination with androgen-deprivation therapy (ADT). Patients in the control group received placebo, ADT, bicalutamide, abiraterone, or a combination that did not include an androgen receptor inhibitor as defined. The primary outcome of interest was relative risk (RR) of falls and fractures among patients receiving androgen receptor inhibitor treatment.
Key Findings
KEY POINTS
- Falls occurred in 525 patients (8%) in the androgen receptor inhibitor group, including those of grade ≥ 3 in 62 (1%), vs 221 patients in the control group (5%), including those of grade ≥ 3 in 28 (0.6%).
- Fractures occurred in 242 patients treated with androgen receptor inhibitors (4%), including those of grade ≥ 3 in 60 (1%), vs 107 patients in the control group (2%), including those of grade ≥ 3 in 23 (0.5%).
Median duration of treatment was 15 months (range = 5.4–20.5 months) in the androgen receptor inhibitor group vs 8 months (range = 5.4–18.3) months in the control group.
Falls occurred in 525 patients (8%) in the androgen receptor inhibitor group, including those of grade ≥ 3 in 62 (1%), vs 221 patients in the control group (5%), including those of grade ≥ 3 in 28 (0.6%). Fractures occurred in 242 patients (4%), including those of grade ≥ 3 in 60 (1%), vs 107 patients (2%), including those of grade ≥ 3 in 23 (0.5%).
The androgen receptor inhibitor group had significantly increased risk of any-grade falls (RR = 1.8, 95% confidence interval [CI] = 1.42–2.24, P < .001) and grade ≥ 3 falls (RR = 1.6, 95% CI = 1.27–2.08, P < .001) vs the control group.
The androgen receptor inhibitor group had significantly increased risk of any-grade fractures (RR = 1.59, 95% CI = 1.35–1.89, P < .001), and grade ≥ 3 fractures (RR = 1.71, 95% CI = 1.12–2.63, P = .01) vs the control group.
The investigators concluded, “Use of androgen receptor inhibitor [therapy] was associated with an increase in falls and fractures in patients with prostate cancer as assessed by a retrospective systematic review and meta-analysis. Further studies are warranted to identify and understand potential mechanisms and develop strategies to decrease falls and fractures associated with androgen receptor inhibitor use.”
Zin W. Myint, MD, of Markey Cancer Center, University of Kentucky, Lexington, is the corresponding author for the JAMA Network Open article.
Disclosure: The study was supported by a grant from the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
