Androgen receptor pathway inhibitors, prostate cancer, and older adults: a global Young International Society of Geriatric Oncology drug review

Abstract

Prostate cancer is a disease of older adults that has undergone a significant therapeutic paradigm shift in the last decade with the emergence of novel androgen receptor pathway inhibitors (ARPis). One of the more commonly used ARPis is enzalutamide. This drug, along with darolutamide and apalutamide, initially received approvals in the metastatic castrate-resistant prostate cancer setting but is now utilized frequently in the metastatic castrate-sensitive and non-metastatic castration-resistant settings. Landmark phase III data illustrating ARPi efficacy in older adults are limited to those with excellent performance status. However, its role in unfit older prostate cancer patients remains to be explored in the context of a narrative review. This first-of-its-kind drug review aims to shed light on the most up-to-date evidence behind the unique toxicity profile of ARPis in the context of geriatric vulnerabilities such as cognitive and functional impairment, along with potential solutions and supporting evidence that exists to circumvent these issues in the vulnerable older adult.

Treatment-Related Cognitive Impairment in Patients with Prostate Cancer: Patients’ Real-World Insights for Optimizing Outcomes

“…Additionally, potential single-agent therapeutic causes of CI and specific cognitive domains remain unclear [ 17 , 27 ]. While ADT may dominate the PCa treatment landscape, it is important to note that treatment-related CI has been documented in PCa and other cancers with multiple therapies, including chemotherapy, hormonal therapy, AR pathway inhibitors, and statins [ 8 , 13 , 15 , 28 – 31 ].…”

“…PCa-TRCI is likely caused by a multitude of factors, and while it is thought to be exacerbated by long-term exposure to treatments such as androgen depravation therapy (ADT), chemotherapy, and novel androgen receptor (AR) pathway inhibitors, it is a clinically complex entity warranting further research [ 3 , 7 , 8 , 13 – 15 ]. PCa-TRCI is an important clinical concern, as CI can negatively impact quality of life (QoL), including work and social relationships, autonomy, and self-confidence, particularly during long-term care [ 8 , 16 – 18 ].…”