STAMPEDE Trial Results for Adjuvant Abiraterone in High-Risk Non-Metastatic Prostate Cancer
For men with high-risk, non-metastatic (M0) prostate cancer receiving definitive radiation therapy, adding abiraterone acetate 1000 mg daily plus prednisone 5 mg daily for 2 years to ADT significantly improves both metastasis-free survival and overall survival compared to ADT alone.
Key Trial Findings
The STAMPEDE trial specifically evaluated abiraterone in high-risk M0 disease, defined as node-positive (N1) OR node-negative with at least 2 of 3 risk factors:
- Stage T3/4
- PSA ≥40 ng/mL
- Gleason score 8-10
Primary Efficacy Results 1, 2
Metastasis-Free Survival:
- Hazard ratio: 0.53 (95% CI 0.44-0.64, p<0.0001)
- 6-year metastasis-free survival: 82% with abiraterone vs 69% with ADT alone
- Median metastasis-free survival: not reached in either group at 72 months median follow-up
Overall Survival:
- Hazard ratio: 0.63 (95% CI 0.48-0.82, p=0.0005) 3
- Hazard ratio: 0.60 (95% CI 0.48-0.73, p<0.0001) in pooled analysis 1
- The survival benefit was larger in men <70 years (HR 0.51) compared to ≥70 years (HR 0.94) 4, 5
Other Outcomes:
- Prostate cancer-specific survival: HR 0.49 (95% CI 0.37-0.65, p<0.0001)
- Biochemical failure-free survival: HR 0.39 (95% CI 0.33-0.47, p<0.0001)
- Progression-free survival: HR 0.44 (95% CI 0.36-0.54, p<0.0001) 1
Treatment Regimen
- Abiraterone acetate 1000 mg orally once daily
- Prednisone or prednisolone 5 mg orally once daily
- Duration: 2 years when combined with curative-intent radiation therapy
- ADT: 24-36 months total duration
- Radiation therapy: 74 Gy in 37 fractions (or equivalent hypofractionated schedule) to prostate and seminal vesicles
Safety Profile
Grade 3-5 Adverse Events 1, 2:
- Occurred in 37-47% with abiraterone vs 29-33% with ADT alone
- Significantly higher in patients ≥70 years (47% vs 33%)
Most Common Serious Toxicities:
- Hypertension: 5-14% (vs 1-2% with ADT alone)
- Elevated liver enzymes (ALT): 6-13% (vs <1% with ADT alone)
- Cardiac disorders: 10% overall
- Grade 5 events: rare but included 9 treatment-related deaths in STAMPEDE (vs 3 with ADT alone)
Critical Monitoring Requirements:
- Blood pressure monitoring throughout treatment
- Hepatic function tests regularly
- Renal function monitoring
- Electrolytes (particularly potassium due to mineralocorticoid excess)
Clinical Application
Who Benefits Most:
- Men <70 years show substantially greater survival benefit
- Node-negative (N0) patients appear to derive particular benefit from locoregional treatment intensification 6
- The benefit persisted across all high-risk subgroups without significant heterogeneity 1
Important Caveats:
- Older men (≥70 years) experience increased toxicity with attenuated survival benefit, requiring careful patient selection 4, 5
- The combination of abiraterone plus enzalutamide showed no additional benefit over abiraterone alone and should NOT be used 1, 7
- Radiation therapy was mandated for node-negative disease and encouraged for node-positive disease in the trial 2
Guideline Recommendations
Current Standard of Care 3:
- External beam radiotherapy plus ADT plus abiraterone-prednisone is recommended for men with very high-risk M0 prostate cancer (Level I, Grade B evidence)
- Men receiving radical RT for very high-risk disease should receive 24-36 months ADT plus 24 months abiraterone-prednisone 3
FDA Approval 8:
- Abiraterone acetate is FDA-approved for metastatic high-risk castration-sensitive prostate cancer, though the M0 indication reflects off-label use based on STAMPEDE data
Alternative Consideration:
- The fine-particle formulation can be administered at 250 mg/day with a low-fat breakfast as an alternative to 1000 mg/day fasting, potentially reducing financial toxicity 5