Androgen Receptor Inhibitors in Patients With Nonmetastatic Castration-Resistant Prostate Cancer

Area of Science:

• Oncology
• Urology
• Pharmacology

Background:

• Novel androgen receptor inhibitors (ARIs) like darolutamide, enzalutamide, and apalutamide are standard treatments for nonmetastatic castration-resistant prostate cancer (nmCRPC).
• Limited data exists comparing the clinical use and tolerability of these ARIs.

Purpose of the Study:

• To compare the clinical use and outcomes of darolutamide, enzalutamide, and apalutamide in patients diagnosed with nmCRPC.
• To evaluate treatment discontinuation and progression to metastatic CRPC (mCRPC) as primary endpoints.

Main Methods:

• Retrospective cohort study analyzing electronic medical records from US urology practices.
• Included 870 patients with nmCRPC who initiated novel ARI treatment between August 2019 and March 2022.
• Compared composite endpoint events (discontinuation or progression to mCRPC), discontinuation rates, and progression rates across the three ARIs.

Main Results:

• Darolutamide was associated with lower proportions of composite endpoint events (37.0%), discontinuation (30.4%), and progression to mCRPC (17.7%) compared to enzalutamide and apalutamide.
• Adjusted analysis revealed a significantly lower risk of composite events, discontinuation, and progression to mCRPC for darolutamide versus enzalutamide and apalutamide.
• No significant differences were observed between enzalutamide and apalutamide for the studied outcomes.

Conclusions:

• Darolutamide appears to offer better tolerability and potentially a clinical effectiveness advantage over enzalutamide and apalutamide in nmCRPC patients.
• The findings suggest darolutamide may be a preferred treatment option, but comparative clinical studies are necessary to confirm these results and guide clinical decisions.