Elisabeth I. Heath, MD, FACP, associate center director of Translational Sciences, lead of the Genitourinary Oncology Multidisciplinary Team, medical director of the Infusion Center, and director of Prostate Cancer Research at Barbara Ann Karmanos Cancer Institute, and professor of oncology at Wayne State University School of Medicine, discusses a remaining challenge in nonmetastatic castration-resistant prostate cancer (CRPC).

The FDA approvals of 3 antiandrogen agents, apalutamide (Erleada), enzalutamide (Xtandi), and darolutamide (Nubeqa) SPARTAN, PROSPER, and ARAMIS trials, respectively, have shifted the treatment paradigm in nonmetastatic CRPC, says Heath.

The CRPC space is one that is recognized based on imaging, says Heath. With improved imaging technology, such as PET scans, micrometastases are now more frequently identified in patients. In the past, these micrometastases may not have been picked up by traditional imaging modalities such as CAT scans or bone scans, explains Heath.

Historically, it was difficult to find sites of micrometastases, despite the patient having a rising prostate specific antigen level, adds Heath. Now the key remaining challenge will be determining how best to categorize these men, concludes Heath

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Elisabeth I. Heath, MD, FACP, discusses a remaining challenge in nonmetastatic castration-resistant prostate cancer.

Dr. Heath on Remaining Challenges in Nonmetastatic CRPC

Elisabeth I. Heath, MD, FACP, associate center director of Translational Sciences, lead of the Genitourinary Oncology Multidisciplinary Team, medical director of the Infusion Center, and director of Prostate Cancer Research at Barbara Ann Karmanos Cancer Institute, and professor of oncology at Wayne State University School of Medicine, discusses apalutamide (Erleada), enzalutamide (Xtandi), and darolutamide (Nubeqa), which have all been approved for use in nonmetastatic castration-resistant prostate cancer (CRPC).

The National Comprehensive Cancer Network has recognized 3 medications for use in nonmetastatic CRPC: apalutamide, enzalutamide, and darolutamide, explains Heath. These agents are approved based on 3 similarly designed phase III studies. Apalutamide was explored in the SPARTAN study, enzalutamide in the PROSPER study, and darolutamide in the ARAMIS study.

The SPARTAN, PROSPER, and ARAMIS studies enrolled at least 1400 to 1500 patients who received the antiandrogens or placebo plus androgen deprivation therapy (ADT) in a 2:1 randomized fashion, according to Heath. The patients enrolled on these trials were men who received standard imaging with a bone or CT scan, no evidence of cancer, and rising prostate-specific antigen, but at a doubling time of less than 10 months—making this patient population a more aggressive group, says Heath.

The trials’ primary objectives were metastasis-free survival and various secondary endpoints, including overall survival. The results from these trials demonstrated that men benefit from apalutamide, enzalutamide, or darolutamide when added to ADT over placebo/ADT, concludes Heath.

Elisabeth I. Heath, MD, FACP, discusses apalutamide, enzalutamide, and darolutamide, which have all been approved for use in nonmetastatic castration-resistant prostate cancer.

Dr. Heath on Recent Approvals in Nonmetastic Prostate Cancer

Elisabeth I. Heath, MD, FACP, associate center director of Translational Sciences, lead of the Genitourinary Oncology Multidisciplinary Team, medical director of the Infusion Center, and director of Prostate Cancer Research at Barbara Ann Karmanos Cancer Institute, and professor of oncology at Wayne State University School of Medicine, discusses the safety profiles of apalutamide (Erleada), enzalutamide (Xtandi), and darolutamide (Nubeqa) in nonmetastatic castration-resistant prostate cancer.

Patients with nonmetastatic disease who receive antiandrogens can experience fatigue, which is consistent with their use in the metastatic castration-resistant setting, says Heath. Regarding the risk of falls and fractures, patients aged 75 or older have a slightly higher incidence of these events; however, it remains unknown if that is due to a balance issue, or the neurologic toxicity of the antiandrogen, says Heath.

Darolutamide shows a lower incidence of neurologic toxicity, which may be a result of its mechanism of action or lower blood—brain barrier penetration, adds Heath.

Lastly, in the phase III PROSPER trial, more cardiovascular deaths were observed in the enzalutamide arm. Therefore, patients who are already experiencing cardiovascular issues may not be optimal candidates for enzalutamide, concludes Heath.

Elisabeth I. Heath, MD, FACP, discusses the safety profiles of apalutamide, enzalutamide, and darolutamide in nonmetastatic castration-resistant prostate cancer.

Elisabeth I. Heath, MD, FACP, Karmanos Cancer Institute

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Dr. Heath on Remaining Challenges in Nonmetastatic CRPC

Dr. Heath on Recent Approvals in Nonmetastic Prostate Cancer

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