Background
Phase III open-label, multinational RCT; 1125 men with metastatic hormone-sensitive prostate cancer (mHSPC). Concurrent early docetaxel was permitted; 16% received docetaxel around randomization.
Interventions and follow up
Arm A: Enzalutamide 160mg daily + testosterone suppression.
Arm B: Standard non-steroidal antiandrogen (bicalutamide, nilutamide, or flutamide) + testosterone suppression.
Primary endpoint: OS; key secondary PSA progression-free survival.
mFollow up: 34mo.
Arm B: Standard non-steroidal antiandrogen (bicalutamide, nilutamide, or flutamide) + testosterone suppression.
Primary endpoint: OS; key secondary PSA progression-free survival.
mFollow up: 34mo.
Results
3-yr OS: 80% vs 72%, arm A vs B; HR 0.67, 95%CI 0.52–0.86; P=.002.
3-yr PSA PFS: 67% vs 37%, arm A vs B; HR 0.39, 95%CI 0.33–0.47; P<.001.
3-yr PSA PFS: 67% vs 37%, arm A vs B; HR 0.39, 95%CI 0.33–0.47; P<.001.
Adverse events
Overall: Serious adverse events 42% vs 34% (arm A vs B); hypertension 8% vs 4%, fatigue 6% vs 1%, syncope 4% vs 1%.
Hematologic (with concurrent docetaxel): Febrile neutropenia 7% vs 6%; neutropenia 6% vs 3%.
Hematologic (with concurrent docetaxel): Febrile neutropenia 7% vs 6%; neutropenia 6% vs 3%.
Conclusions
Enzalutamide improved OS and PSA progression-free survival versus a standard non-steroidal antiandrogen in men with metastatic hormone-sensitive prostate cancer.
Key Limitations
Open-label design; comparator was a first-generation antiandrogen rather than ADT alone, and the OS benefit of adding enzalutamide to concurrent docetaxel was not clearly demonstrated at the interim analysis.
Clinical Context
FDA approved enzalutamide for mHSPC in 2019. With ARCHES, ENZAMET established enzalutamide + ADT as a standard first-line option for metastatic hormone-sensitive prostate cancer in ASCO/ESMO guidelines.