Dr Matthew Smith discusses next generation androgen receptor inhibitors and data from clinical trials with these agents.
Matthew R. Smith, MD, PhD: In my practice, androgen receptor pathway inhibitors are a mainstay of treatment for patients with non-metastatic and metastatic castration-resistant prostate cancer. This class of drugs has brought approval across a wide spectrum of clinical disease states from metastatic castration-sensitive prostate cancer (mCSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC).
There are currently 4 approved androgen receptor pathway inhibitors in the United States: 3 anti-androgens—apalutamide, enzalutamide, and darolutamide—and an androgen receptor pathway inhibitor, abiraterone acetate. The efficacy of these agents, while rarely studied head-to-head, appears remarkably similar based on cross-trial comparisons. The choice of agents tends to focus on the expected tolerability in an individual patient. In non-metastatic castration-resistant prostate cancer, for example, there are 3 approved drugs: apalutamide, enzalutamide, and darolutamide. They were approved based on pivotal studies of remarkably similar design and, candidly, efficacy results that are highly overlapping with marked improvements in metastasis-free survival in each of the 3 trials and in overall survival benefit in the final survival analysis for each of those studies.
In contrast to the 2 other drugs, darolutamide does not cross the blood-brain barrier well and may lack some of the CNS side effects associated with the other drugs. Consistent with that nonclinical information, cross-trial comparison between the SPARTAN, PROSPER, and ARAMIS trials suggest that darolutamide lacks some of the CNS [central nervous system] toxicity with what appears to be less fatigue and no risk for falls or fractures. This case illustrates the importance of having choices so a patient who was intolerant of enzalutamide was able to still benefit from an androgen receptor pathway inhibitor by subsequent treatment with darolutamide. He tolerated that treatment well and continued to respond.
Transcript edited for clarity.
Case: A 82-Year-Old Man with Metastatic Castration-Resistant Prostate Cancer