Absolute Benefit of ADT + Abiraterone Therapy in Metastatic Hormone-Sensitive Prostate Cancer
The addition of abiraterone acetate plus prednisone to ADT in patients with metastatic hormone-sensitive prostate cancer provides a 14% absolute improvement in 3-year survival and a 28% absolute improvement in 3-year progression-free survival compared to ADT alone. 1
Survival Benefits
A systematic review and meta-analysis using the Framework for Adaptive Meta-Analyses (FAME) pooled data from 2,201 men with metastatic disease from the STAMPEDE and LATITUDE trials, showing that adding abiraterone to ADT reduced the risk of death by 38% (HR, 0.62; 95% CI, 0.53 to 0.71), resulting in a 14% absolute improvement in 3-year survival 1
The LATITUDE trial's final analysis after a median follow-up of 51.8 months demonstrated that median overall survival was significantly longer in the abiraterone acetate plus prednisone group (53.3 months) compared to the placebo group (36.5 months), with a hazard ratio of 0.66 (95% CI, 0.56-0.78; p<0.0001) 2
The STAMPEDE trial showed similar results with a hazard ratio of 0.63 (95% CI, 0.52 to 0.76; p<0.001) for overall survival, confirming the substantial survival benefit 3
Progression-Free Survival Benefits
The addition of abiraterone to ADT reduced the risk of radiographic or clinical progression by 55% (HR, 0.45; 95% CI, 0.40 to 0.51), resulting in a 28% absolute improvement at 3 years 1
In the LATITUDE trial, the median length of radiographic progression-free survival was 33.0 months in the abiraterone group compared to 14.8 months in the placebo group (HR, 0.47; 95% CI, 0.39 to 0.55; p<0.001) 4
Quality of Life Benefits
ADT plus abiraterone showed significant improvements in quality of life measures compared to ADT alone 1:
- 37% risk reduction in pain intensity progression (BPI-SF) (HR, 0.63; 95% CI, 0.52 to 0.47; p<0.001)
- 53% risk reduction in fatigue (BFI) (HR, 0.65; 95% CI, 0.53 to 0.81; p=0.0001)
- 15% risk reduction in overall quality of life deterioration (FACT-P) (HR, 0.85; 95% CI, 0.74 to 0.99; p=0.0322)
A network meta-analysis comparing ADT plus abiraterone versus ADT plus docetaxel found that abiraterone plus ADT showed improved quality of life compared with docetaxel plus ADT for at least 1 year of therapy, with results being more pronounced at 3 months 5
Patient Selection and Recommendations
The American Society of Clinical Oncology (ASCO) recommends abiraterone combination with ADT for men with newly diagnosed metastatic non-castrate disease on the basis of prolonging life relative to ADT alone 1
The National Comprehensive Cancer Network (NCCN) strongly recommends ADT with treatment intensification (including abiraterone) for patients with metastatic castration-sensitive prostate cancer, and discourages the use of ADT monotherapy unless there are clear contraindications to combination therapy 1
The LATITUDE trial specifically demonstrated benefit in high-risk patients defined as having at least two of the following: Gleason score 8–10, ≥3 bone metastases, and visceral metastases 1, 2
Dosing and Administration
The recommended dose is abiraterone acetate 1,000 mg orally once daily on an empty stomach, with prednisone 5 mg orally twice daily 6, 7
Continuous ADT should be maintained throughout treatment to maintain castrate levels of testosterone (<50 ng/dL) 6
Adverse Events
More grade 3-4 acute cardiac, vascular, and hepatic toxicities were seen with abiraterone plus ADT, but there was no statistically significant excess of deaths 1
Common side effects (>5%) include joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flushes, diarrhea, hypertension, and fatigue 1
Regular monitoring is essential for liver function tests, serum potassium and phosphate levels, and blood pressure readings 7
Practical Considerations
The absolute benefit of abiraterone plus ADT must be weighed against the increased risk of side effects and the cost of treatment 1
Spironolactone should be avoided as it can interfere with abiraterone's mechanism of action 7
For patients who develop progression on abiraterone, switching from prednisone to dexamethasone 1 mg/day can be considered 7