Next-Generation Androgen Receptor-Signaling Inhibitors for Prostate Cancer: Considerations for Older Patients

Prostate cancer is common, particularly in older patients, as the risk of getting prostate cancer increases with age. Cancer therapy brings unique challenges in older patients, as this population is vulnerable to many side effects and drug interactions, and they have varying degrees of frailty, which may limit the use of these therapies. The US FDA has recently approved several novel next-generation hormonal therapies for patients with various stages of prostate cancer, giving patients more treatment options. These therapies (e.g., apalutamide, enzalutamide, darolutamide, and abiraterone) have unique side effects that the practitioner must consider when evaluating therapeutic treatments in any patient, and these side effects also affect older patients differently. Here, we review the mechanism of action and metabolism of the next-generation hormonal therapies; report efficacy and safety data from trials of these agents in non-metastatic castration-resistant prostate cancer, metastatic hormone-sensitive prostate cancer, and metastatic castration-resistant prostate cancer; and discuss the intricacies of treating older men with prostate cancer. Key takeaways include the fact that enzalutamide and apalutamide may increase the risk of falls and fractures in older patients. Abiraterone requires the concurrent use of low-dose glucocorticoids, which can lead to side effects in older patients. Lastly, drug–drug interactions should be considered in older patients using multiple medications.