Falls and fractures in men with prostate cancer taking second-generation androgen receptor antagonists: A retrospective chart review

Abstract

Introduction

Second-generation androgen receptor antagonists, including enzalutamide, apalutamide, and darolutamide, are commonly used to treat metastatic and non-metastatic prostate cancer. Although these medications are typically well-tolerated, falls were reported in 4.2–15.6% of patients and fractures in 4.2–11.7% of patients enrolled in the phase III clinical trials evaluating these drugs in prostate cancer. However, post-marketing studies have reported a lower incidence than reported in clinical trials. The objective of this study is to determine the prevalence of falls and fractures in patients with prostate cancer receiving second-generation androgen receptor antagonists at UConn Health and identify potential risk factors associated with falls and fractures in these patients.

Methods

A retrospective chart review involving patients with prostate cancer treated with darolutamide, enzalutamide, or apalutamide from March 1, 2022, to March 31, 2023, at UConn Health Carole & Ray Neag Comprehensive Cancer Center. Data recorded includes basic demographics, history of fall or fracture, presence of metastases, fall risk, history of osteoporosis, prescribed second-generation androgen receptor antagonist, and other comorbidities. Data was evaluated using descriptive statistics.

Results

Twenty-six men were included, all of whom were receiving enzalutamide. At baseline, 96.1% of patients had bone metastases, 15.4% had osteoporosis, 15.4% had osteopenia, and 34.6% had neuropathy. The incidence of falls was 19.2% and the incidence of fractures was 26.9%. The mean length of therapy at time of a fall was 19.44 months (range, 6–31 months). The mean length of therapy at time of a fracture was 19 months (range, 1–33 months). In patients experiencing fall, 100% had arthralgia, 60% had neuropathy, 40% had a gait problem, 40% had hypertension, and 80% of them were at risk of fall. In patients experiencing fracture, 28.6% had osteoporosis, 42.9% had osteopenia, 100% had bone metastases, and 57.1% were on denosumab at time of fracture.

Conclusion

The prevalence of falls and fractures in patients receiving enzalutamide were higher in this retrospective chart review than reported in clinical trials and post-marketing studies. This could be due to the small patient population or the patient's comorbidities such as osteoporosis, bone metastases, or neuropathy. Fall/fracture risk with enzalutamide and other risk factors for fall and fracture should be considered when discussing treatment and developing a monitoring plan.