Enzalutamide for High-Risk Metastatic Prostate Adenocarcinoma to Bone
Enzalutamide is a Category 1, preferred treatment option for metastatic castration-resistant prostate cancer (mCRPC) with bone metastases, supported primarily by the PREVAIL trial, which demonstrated a 29% reduction in mortality risk and significantly improved progression-free survival. 1
Primary Evidence: The PREVAIL Trial
The pivotal evidence comes from the PREVAIL trial (NCT01212991), a randomized, double-blind, phase III study that enrolled 1,717 chemotherapy-naïve patients with metastatic CRPC. 2 This trial was stopped early at interim analysis due to clear benefit in the treatment arm. 1
Key Efficacy Outcomes from PREVAIL:
Overall Survival: Median OS was 35.3 months with enzalutamide versus 31.3 months with placebo (HR 0.71; 95% CI 0.60-0.84; P<0.001), representing a 29% reduction in death risk 1, 2
Radiographic Progression-Free Survival: 65% of enzalutamide patients remained progression-free at 12 months versus only 14% on placebo (HR 0.19; 95% CI 0.15-0.23; P<0.001), representing an 81% risk reduction 2
Time to Chemotherapy Initiation: Median 28.0 months with enzalutamide versus 10.8 months with placebo (HR 0.35; 95% CI 0.30-0.40) 2, 3
Time to First Skeletal-Related Event: Significantly delayed with enzalutamide (HR 0.72; P<0.001) 1, 2
PSA Response: 78% of patients achieved ≥50% PSA decline with enzalutamide versus 3% with placebo 2
Supporting Evidence and Comparative Trials
The TERRAIN and STRIVE trials provide additional evidence demonstrating enzalutamide's superiority over bicalutamide in treatment-naïve mCRPC:
TERRAIN study (n=375): Median PFS 15.7 months with enzalutamide versus 5.8 months with bicalutamide (HR 0.44; 95% CI 0.34-0.57) 1, 4
STRIVE trial (n=396): 76% reduction in progression or death risk with enzalutamide versus bicalutamide (HR 0.24; 95% CI 0.18-0.32) 1, 4
Guideline Recommendations
The NCCN (National Comprehensive Cancer Network) designates enzalutamide as a Category 1, preferred treatment option for patients with mCRPC without prior novel hormone therapy. 1, 4 This represents the highest level of evidence and consensus that the intervention is appropriate.
Safety Profile
The most common adverse events from PREVAIL include:
- Fatigue: 33% versus 14% with placebo 1
- Hypertension: 12% versus 5% with placebo 1
- Major adverse cardiovascular events: 5% versus 3% with placebo 1
- Mental impairment disorders: 5% versus 2% with placebo 1
- Seizure risk: 0.6-0.9%, requiring permanent discontinuation if occurs 4, 5
Important caveat: Enzalutamide should be permanently discontinued immediately if seizure occurs during treatment. 5
Practical Administration
- Dosing: 160 mg orally once daily 1, 2
- No food restrictions for intake 1
- Concurrent prednisone is permitted but not required 1
- Continue LHRH agonist/antagonist therapy when using enzalutamide 4
Asian Population Validation
A separate Asian multiregional study (NCT02294461) with 388 patients confirmed enzalutamide's efficacy in chemotherapy-naïve Asian patients with mCRPC, showing median time to PSA progression of 8.31 months versus 2.86 months with placebo (HR 0.38; P<0.0001). 6 This validates the PREVAIL findings across diverse populations.
Cost Consideration
While enzalutamide is more expensive than bicalutamide, the superior efficacy profile and improved survival outcomes support its use as first-line therapy in appropriate patients. 1, 4