What is the role of Abiraterone (abiraterone acetate) in the treatment of non-castrated (intact) prostate cancer?

Role of Abiraterone in Non-Castrated Prostate Cancer

Abiraterone acetate in combination with prednisone/prednisolone and androgen deprivation therapy (ADT) should be offered as a standard of care for men with high-risk metastatic non-castrated prostate cancer. 1

Evidence-Based Treatment Algorithm

Patient Selection for Abiraterone Therapy

1. High-Risk Metastatic Disease (strongest recommendation):

   • Patients with high-risk de novo metastatic non-castrated prostate cancer per LATITUDE criteria 1:
     • At least two of the following:
       • Gleason score ≥8
       • At least three bone lesions
       • Presence of measurable visceral disease

2. Lower-Risk Metastatic Disease (moderate recommendation):

   • Patients with lower-risk de novo metastatic non-castrated prostate cancer may also benefit 1
   • Evidence from STAMPEDE trial supports use in this population with a moderate strength recommendation

3. Locally Advanced Non-Metastatic Disease:

   • The combination of ADT plus abiraterone and prednisolone should be considered for men with non-castrate locally advanced non-metastatic prostate cancer who have undergone radiotherapy 1

Recommended Regimen

• Dosage: Abiraterone 1,000 mg with prednisolone or prednisone 5 mg once daily 1
• Administration: Take on an empty stomach
• Duration: Continue until progressive disease is documented 1

Comparative Efficacy

Abiraterone plus ADT has demonstrated significant survival benefits in non-castrated prostate cancer:

• Overall Survival: In the LATITUDE trial, median overall survival was not reached in the abiraterone group vs. 34.7 months in the placebo group (HR 0.62; 95% CI, 0.51-0.76) 2
• Radiographic Progression-Free Survival: 33.0 months with abiraterone vs. 14.8 months with placebo (HR 0.47; 95% CI, 0.39-0.55) 2
• Secondary Endpoints: Significant improvements in time to pain progression, next subsequent therapy, initiation of chemotherapy, and PSA progression 2

Alternative Treatment Options

Docetaxel, enzalutamide, or apalutamide, each administered with ADT, represent separate standards of care for non-castrate metastatic prostate cancer 1. The choice between these options should be based on:

• Patient comorbidities
• Toxicity profiles
• Quality of life considerations
• Drug availability and cost

Important Considerations and Caveats

• Formulation Specificity: Only the original FDA-approved formulation of abiraterone acetate (1,000 mg) should be used in the non-castrated setting 1
• Alternative Dosing Not Recommended: The panel does not support:
  • Using micronized abiraterone in the non-castrated setting
  • Using the 250 mg dose with a low-fat breakfast 1
• Combination Therapy: Currently, the use of abiraterone in combination with other agents (docetaxel, enzalutamide, apalutamide) or in sequence cannot be recommended due to lack of evidence 1
• Monitoring: Regular monitoring for adverse events is essential, particularly hypertension and hypokalemia, which occur at higher rates with abiraterone 2

Safety Profile

Common adverse events with abiraterone plus prednisone include:

• Hypertension (grade 3 more common)
• Hypokalemia (grade 3 more common)
• Peripheral edema
• Urinary tract infections 3

These mineralocorticoid-related adverse events are generally manageable with basic medical interventions 3.

By following this evidence-based approach to abiraterone therapy in non-castrated prostate cancer, clinicians can optimize treatment outcomes while minimizing adverse effects, ultimately improving survival and quality of life for these patients.