Dr. Higano on the Toxicity of Androgen Receptor Inhibitors in CRPC

Celestia Higano, MD, FACP, member, Clinical Research Division, Fred Hutchinson Cancer Research Center, professor, Department of Medicine and Urology, University of Washington, Seattle Cancer Care Alliance, discusses the toxicity of androgen receptor (AR) inhibitors in castration-resistant prostate cancer (CRPC).

Enzalutamide (Xtandi) and apalutamide (Erleada) both cross the blood-brain barrier. However, data from the phase III ARAMIS trial suggested that darolutamide does not penetrate the blood-brain barrier as well as these earlier-generation inhibitors, says Higano.

The thought is that penetration of the blood-brain barrier is partially responsible for some of the common adverse events (AEs) seen with AR inhibitors like fatigue, weakness, and falls, Higano says. It is hard to explain some of the other toxicities seen with these drugs, but patients have complained of bizarre dreams or strange thoughts, for example. Higano notes that if these AEs are associated with AR inhibitors crossing the blood-brain barrier, they may be less prevalent with darolutamide. However, it is going to take some time before the field knows for certain if darolutamide is superior to the 2 FDA-approved AR inhibitors.