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.

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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 inhibitors in castration-resistant prostate cancer.

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 role of PARP inhibitors in the treatment of patients with prostate cancer.

Investigators initially thought that PARP inhibitors would be limited to the small subset of patients who express DNA repair gene defects. However, going back to the original 

 article exploring PARP inhibitors in this space, about 6% of patients responded to therapy who did not have a DNA repair gene defect. This suggests that PARP inhibitors may extend beyond the specific precision medicine approach that was originally associated with this therapy.

For example, Higano says, PARP inhibitors may have benefit in patients whose tumors express a transcription of factors that are important in blocking the androgen receptor. In general, these drugs could have a dual role in the treatment of patients with prostate cancer.

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 role of PARP inhibitors in prostate cancer.

Celestia Higano, MD, FACP

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

Dr. Higano on Role of PARP Inhibitors in Prostate Cancer