Background
Phase 2 open-label RCT; N=227 low- or intermediate-risk localized prostate cancer; enzalutamide plus active surveillance vs active surveillance alone.
Interventions and follow up
Arm A: Enzalutamide 160 mg PO daily x 1 year + active surveillance
Arm B: Active surveillance alone
Primary endpoint: Time to pathological or therapeutic prostate cancer progression
mFollow up: ~16.5 mo
Arm B: Active surveillance alone
Primary endpoint: Time to pathological or therapeutic prostate cancer progression
mFollow up: ~16.5 mo
Results
1yr pathological/therapeutic progression: 7.9% vs 23.0%, OR 0.30, 95% CI 0.11–0.60, P<.01.
2yr pathological/therapeutic progression: 16.0% vs 16.4%, OR 0.90, 95% CI 0.36–2.24, P=.81 (NS).
2yr pathological/therapeutic progression: 16.0% vs 16.4%, OR 0.90, 95% CI 0.36–2.24, P=.81 (NS).
Adverse events
Any AE: 92% vs 54.9% (A vs B).
Constitutional: fatigue 55.4% vs 3.5%.
Breast/hormonal: gynecomastia 36.6% vs 1.8%; nipple pain 30.4% vs 0; breast tenderness 25.9% vs 0.9%.
Sexual: erectile dysfunction 17.9% vs 1.8%.
Constitutional: fatigue 55.4% vs 3.5%.
Breast/hormonal: gynecomastia 36.6% vs 1.8%; nipple pain 30.4% vs 0; breast tenderness 25.9% vs 0.9%.
Sexual: erectile dysfunction 17.9% vs 1.8%.
Conclusions
Enzalutamide reduced short-term progression in low/intermediate-risk prostate cancer on active surveillance, but the 1-year benefit was not durable at 2 years, with a notable toxicity and cost burden.
Key Limitations
Open-label phase 2; surrogate composite endpoint (pathological/therapeutic progression) not OS or metastasis; benefit not sustained at 2 years; short follow-up; substantial AE and cost burden for indolent disease; no validated long-term clinical benefit.
Clinical Context
Enzalutamide is not FDA/EMA approved in the active-surveillance setting; active surveillance remains standard of care for low/favorable-intermediate-risk localized prostate cancer per ASCO/ESMO. ENACT does not change practice; antiandrogen therapy is not recommended over surveillance for indolent disease.