Role of Abiraterone in Metastatic Castrate-Sensitive Prostate Cancer
Abiraterone acetate 1000 mg daily plus prednisone 5 mg daily combined with androgen deprivation therapy (ADT) is a Category 1, preferred treatment option for all patients with metastatic castrate-sensitive prostate cancer (mCSPC) and should be initiated at diagnosis rather than waiting for castration resistance. 1
Treatment Recommendation and Evidence Base
ADT monotherapy is strongly discouraged in mCSPC unless clear contraindications to combination therapy exist. 1 The addition of abiraterone to ADT represents treatment intensification that fundamentally changes outcomes:
Survival Benefits
Median overall survival improves from 36.5 months with ADT alone to 53.3 months with abiraterone plus ADT (HR 0.66; 95% CI 0.56-0.78; P<0.0001) based on the final LATITUDE trial analysis at 51.8 months median follow-up 1
The LATITUDE trial specifically enrolled high-risk patients defined as having at least 2 of the following: Gleason score 8-10, ≥3 bone metastases, or visceral metastases 1
Three-year overall survival rates increased from 49% to 66% in the abiraterone group 1
Secondary Outcome Improvements
All secondary endpoints favor abiraterone treatment 1:
- Radiographic progression-free survival: 33.0 months versus 14.8 months (HR 0.47; 95% CI 0.39-0.55; P<0.001) 2
- PSA progression: delayed from 7.4 months to 33.2 months 1
- Time to pain progression: significantly delayed 1
- Time to chemotherapy initiation: significantly delayed 1
Specific Dosing and Administration
The FDA-approved regimen is abiraterone acetate 1000 mg (four 250-mg tablets) once daily on an empty stomach plus prednisone 5 mg once daily. 1, 3
Critical Administration Requirements
Abiraterone must be taken on an empty stomach (at least 1 hour before or 2 hours after food) due to significantly higher drug exposure with food 3
Prednisone 5 mg daily is mandatory to manage mineralocorticoid excess from CYP17A1 inhibition 1
Spironolactone must not be used for mineralocorticoid management as it interferes with abiraterone's mechanism of action 3, 4
ADT Options for Combination Therapy
The following ADT approaches can be combined with abiraterone 1:
- Orchiectomy plus abiraterone
- LHRH agonist plus abiraterone
- LHRH antagonist plus abiraterone
For patients with weight-bearing bone metastases receiving LHRH agonists, antiandrogen therapy should precede or be coadministered for at least 7 days to prevent testosterone flare 1
Mandatory Monitoring Protocol
Baseline Assessment 3
- Blood pressure measurement
- Serum potassium and phosphate levels
- Liver function tests (AST, ALT)
- Cardiac evaluation in patients with cardiovascular risk factors
Ongoing Monitoring 3
- Monthly liver function tests (7% risk of grade 3-5 hepatotoxicity)
- Monthly serum potassium and phosphate monitoring
- Regular blood pressure checks (21% risk of grade 3-4 hypertension)
- Symptom-directed cardiac assessment
Adverse Event Profile and Management
Common Mineralocorticoid-Related Effects 1, 3
- Hypertension: 21% grade 3-4, managed with antihypertensives
- Hypokalemia: 12% grade 3-4, requiring potassium supplementation
- Peripheral edema: 28% any grade, typically mild
Other Adverse Events 1
- Fatigue and hot flushes (hormonal effects)
- Hepatotoxicity requiring monitoring
- Cardiac events including atrial fibrillation (rare but increased)
- Overall discontinuation rate due to adverse events: 12% 1
Adverse events are generally mild (grade 1-2) and manageable with appropriate monitoring and supportive care. 1
Quality of Life Improvements
Patient-reported outcomes demonstrate significant benefits with abiraterone addition 1, 3:
- Improved pain intensity progression
- Reduced fatigue
- Better functional status
- Improved prostate cancer-related symptoms
- Enhanced overall health-related quality of life
Critical Contraindications and Pitfalls
Absolute Contraindications
- Abiraterone must not be combined with radium-223 as this increases fracture risk without improving symptomatic skeletal event-free survival 3
Important Limitations
Only 27% of placebo-treated patients in LATITUDE received abiraterone or enzalutamide at progression, which may overestimate the survival benefit of early versus delayed treatment 1
The LATITUDE trial specifically enrolled high-risk patients, so benefits may differ in lower-risk mCSPC populations 1
Alternative Treatment Intensification Options
While abiraterone is Category 1 preferred, other doublet therapy options exist 1:
- ADT with apalutamide (Category 1)
- ADT with enzalutamide (Category 1)
- ADT with docetaxel (Category 1)
Triplet therapy options include ADT with docetaxel plus abiraterone or darolutamide (Category 1) 1
Treatment Duration
Abiraterone should be continued until disease progression to castration-resistant prostate cancer or unacceptable toxicity. 1, 2 The median duration of benefit in LATITUDE was 33.2 months for radiographic progression-free survival 1