When is abiraterone used in the treatment of metastatic castration-resistant prostate cancer in adult males?

When Abiraterone is Used in Prostate Cancer

Abiraterone acetate plus prednisone should be offered to men with metastatic castration-resistant prostate cancer (mCRPC), both before and after chemotherapy, as it demonstrates improved overall survival, quality of life, and a favorable benefit-harm balance. 1

Primary Indications for Abiraterone

Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Pre-Chemotherapy Setting (First-Line):

• Abiraterone is a Category 1 recommendation for asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients. 2, 3
• Median radiographic progression-free survival improves dramatically from 8.3 months with placebo to 16.5 months with abiraterone (HR 0.53; 95% CI 0.45-0.62; P<0.001). 1
• Overall survival shows a trend toward improvement (median not reached vs. 27.2 months; HR 0.75; 95% CI 0.61-0.93). 1
• Delays pain progression (26.7 vs. 18.4 months; HR 0.82; P=0.049) and functional decline (12.7 vs. 8.3 months; HR 0.78; P=0.003). 1

Post-Chemotherapy Setting (After Docetaxel):

• For men who previously received docetaxel, abiraterone significantly improves overall survival from 11.2 to 15.8 months (HR 0.74; 95% CI 0.64-0.86; P<0.001). 1
• Median radiographic progression-free survival extends from 3.6 to 5.6 months (HR 0.66; P<0.001). 1
• PSA response rate is 29.5% vs. 5.5% with placebo (P<0.001). 1
• Median time to functional decline improves from 3 to 5 months (P<0.001). 1

Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

High-Risk Disease at Initial Diagnosis:

• Abiraterone plus prednisone combined with ADT is a Category 1 recommendation for newly diagnosed metastatic castration-sensitive prostate cancer with high-risk features. 2, 4
• The LATITUDE trial demonstrated median overall survival of 53.3 months vs. 36.5 months with ADT alone (HR 0.66; 95% CI 0.56-0.78; P<0.0001). 4
• Median radiographic progression-free survival extends from 14.8 to 33.0 months (HR 0.47; 95% CI 0.39-0.55; P<0.001). 5
• Delays time to pain progression, chemotherapy initiation, and PSA progression (all P<0.001). 5

Non-Metastatic CRPC (Limited Role)

• Abiraterone may be offered as an option to select patients with non-metastatic CRPC at high risk for developing metastatic disease who refuse or cannot receive standard therapies (apalutamide, enzalutamide, darolutamide) and are unwilling to accept observation alone. 1
• This is an Option-level recommendation (Grade C evidence) based on extrapolation from metastatic disease data, not direct evidence in this population. 1

Dosing and Administration

Standard Dosing:

• Abiraterone acetate 1,000 mg orally once daily plus prednisone 5 mg orally twice daily. 1, 6
• Must be taken on an empty stomach (at least 1 hour before or 2 hours after meals) due to significantly increased drug exposure with food. 4, 6
• Continue concurrent ADT (GnRH agonist/antagonist) or maintain castrate status if post-orchiectomy. 1, 6

Alternative Low-Dose Regimen:

• Abiraterone 250 mg once daily with a low-fat breakfast is a Category 2B alternative to reduce financial toxicity and improve compliance. 2, 3

Dose Modifications:

• For baseline moderate hepatic impairment (Child-Pugh Class B), reduce starting dose to 250 mg once daily. 6
• For hepatotoxicity during treatment, hold until recovery, then consider retreatment at reduced dose; discontinue if severe hepatotoxicity develops. 6

Mandatory Monitoring Requirements

Baseline Assessment:

• Blood pressure, serum potassium, liver function tests, and cardiac evaluation. 3, 4

Ongoing Monitoring (At Least Monthly):

• Blood pressure and symptoms of fluid retention. 2, 6
• Serum potassium and correction of hypokalemia. 2, 6
• Liver function tests (monthly initially). 3, 4
• Blood glucose in diabetic patients taking thiazolidinediones or repaglinide due to severe hypoglycemia risk. 6

Expected Adverse Events and Management

Mineralocorticoid-Related Effects (Most Common):

• Hypertension (21% grade 3-4), hypokalemia (12% grade 3-4), and peripheral edema (28% any grade). 4
• Control hypertension and correct hypokalemia before initiating treatment. 6
• Critical pitfall: Do NOT use spironolactone for mineralocorticoid management as it interferes with abiraterone's mechanism. 4

Other Common Adverse Events (>10%):

• Fatigue, arthralgia, nausea, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache. 6
• Hepatotoxicity (7% grade 3-5 liver toxicity). 3
• Cardiac disorders (10% severe hypertension or cardiac events). 3

Overall Tolerability:

• Discontinuation rate due to adverse events is approximately 12%. 3
• Low rate of grade 3-4 adverse events overall, with no statistically significant differences from control in pre-chemotherapy trials. 1

Age-Related Considerations

Elderly Patients (≥70 Years):

• The survival benefit is larger in men <70 years (HR 0.51) compared to older men (HR 0.94). 3
• Older men experience significantly higher rates of grade 3-5 adverse events (47% vs. 33%) and treatment-related deaths. 3
• Exercise increased caution and closer monitoring in elderly patients, particularly those with cardiovascular comorbidities. 3

Critical Contraindications and Drug Interactions

Absolute Contraindications:

• Do NOT combine abiraterone with radium-223, as this increases fracture risk without improving symptomatic skeletal event-free survival. 4, 6

Drug Interactions:

• Avoid concomitant strong CYP3A4 inducers; if unavoidable, increase abiraterone dosing frequency. 6
• Avoid co-administration with CYP2D6 substrates with narrow therapeutic index; if unavoidable, reduce the CYP2D6 substrate dose. 6

Treatment Selection Algorithm

For Newly Diagnosed Metastatic Castration-Sensitive Prostate Cancer:

1. Assess for high-risk features (visceral metastases, ≥3 bone lesions with ≥1 beyond vertebral bodies/pelvis, Gleason ≥8)
2. If high-risk → Offer ADT + abiraterone + prednisone 4
3. If not high-risk → Consider ADT alone or ADT + docetaxel based on patient factors

For Metastatic Castration-Resistant Prostate Cancer:

1. Confirm castrate testosterone levels (<50 ng/dL) and disease progression
2. Assess symptom burden:
   • Asymptomatic/mildly symptomatic, chemotherapy-naïve → Offer abiraterone or enzalutamide as first-line 2, 3
   • Symptomatic, good performance status → Offer abiraterone, enzalutamide, or docetaxel 1
   • Post-docetaxel progression → Offer abiraterone (if not previously used), enzalutamide, or cabazitaxel 1
3. Choice between abiraterone and enzalutamide should be based on comorbidities (favor enzalutamide if significant cardiovascular disease or hypertension), side effect profiles, and patient preference. 3

For Non-Metastatic CRPC:

1. First-line: Offer apalutamide, enzalutamide, or darolutamide (standard therapies with proven metastasis-free survival benefit)
2. If patient refuses or cannot tolerate standard therapies → Consider observation with continued ADT
3. If patient refuses observation → May offer abiraterone (extrapolated benefit, no direct evidence) 1