Dr Armstrong on Androgen Receptor Inhibitors for Prostate Cancer

Here, Andrew J. Armstrong, MD, MSc, medical oncologist at Duke Cancer Institute, discusses the role of androgen receptor pathway inhibitors (ARPIs) in prostate cancer.

Enzalutamide (Xtandi), much like its counterparts apalutamide (Erleada), abiraterone (Zytiga), and darolutamide (Nubeqa), belongs to a crucial class of drugs known as ARPIs. These medications are a cornerstone of modern prostate cancer treatment, specifically targeting the signaling pathways that fuel the growth and proliferation of cancer cells. The primary mechanism of action for these ARPIs involves blocking the androgen receptor, a protein that, when activated by hormones like testosterone, promotes the growth of prostate cancer. By disrupting this pathway, ARPIs effectively slow or halt the progression of the disease.

In clinical practice, ARPIs are most commonly utilized in the metastatic, hormone-sensitive prostate cancer setting. This is a critical stage of the disease where the cancer has spread beyond the prostate gland to other parts of the body, and it still responds to hormone-blocking therapies. This category includes two distinct patient populations. The first are individuals diagnosed with de novo metastatic disease, meaning the cancer has already metastasized at the time of their initial diagnosis. The second group consists of patients who experience a relapse after receiving local therapy, such as surgery (prostatectomy) or radiation. These patients initially had localized disease but later developed metastatic relapse.

For both of these patient groups, the addition of an ARPI to their treatment regimen has been shown to significantly improve outcomes. A key benefit of these agents, including enzalutamide, is their ability to improve overall survival. The efficacy of enzalutamide in this context was definitively established by the ARCHES study. This landmark clinical trial demonstrated that enzalutamide, when used in combination with standard androgen deprivation therapy (ADT), significantly prolonged the lives of men with metastatic hormone-sensitive prostate cancer. The compelling results of the ARCHES study ultimately led to the approval of enzalutamide for this specific indication in 2019, solidifying its place as a standard-of-care treatment option. The introduction of these potent ARPIs has revolutionized the management of metastatic prostate cancer, offering patients improved survival and a better quality of life.