Enzalutamide vs Abiraterone in Prostate Cancer

Initial Treatment Selection for mCRPC

• The American Urological Association recommends enzalutamide and abiraterone as Grade A standard options for treatment-naïve metastatic castration-resistant prostate cancer (mCRPC) patients with good performance status and no prior docetaxel chemotherapy 1, 2
• Enzalutamide binds androgen receptor with 5-8 fold higher affinity than bicalutamide, inhibits DNA binding, blocks nuclear translocation, and has reduced agonist activity 1

Optimal Sequencing Strategy

• The National Comprehensive Cancer Network (NCCN) guidelines recommend starting with abiraterone followed by enzalutamide if both agents will be used sequentially, as this provides superior outcomes compared to the reverse sequence 4, 5, 6

Cross-Resistance Considerations

• The NCCN guidelines advise against switching from enzalutamide to abiraterone or vice versa in patients who have already received one agent for mCRPC due to cross-resistance 4, 5, 6
• Cabazitaxel is the preferred option after progression on either agent plus docetaxel, with a radiographic PFS of 8.0 months compared to 3.7 months for switching between enzalutamide and abiraterone (HR=0.54, p<0.0001) 4, 5, 6

Adverse Event Profiles

• Abiraterone requires monitoring for mineralocorticoid excess, hepatotoxicity, and cardiac events, with an overall discontinuation rate of 12% 7, 3
• Enzalutamide is associated with fatigue, seizure risk, diarrhea, and hot flashes 8

Practical Dosing Considerations

• Abiraterone can be administered at a standard dose of 1,000mg daily on an empty stomach or as a cost-saving alternative at 250mg daily with a low-fat breakfast 3, 9
• Enzalutamide is administered at a dose of 160mg once daily 1