Background
Phase III double-blind RCT; 1052 men with metastatic castration-sensitive prostate cancer (mCSPC) across the disease-volume and risk spectrum. Prior docetaxel was allowed; 10.7% had received docetaxel before randomization.
Interventions and follow up
Arm A: Apalutamide 240mg daily + ADT.
Arm B: Placebo + ADT.
Primary endpoints: Radiographic PFS and OS.
mFollow up: 22.7mo.
Arm B: Placebo + ADT.
Primary endpoints: Radiographic PFS and OS.
mFollow up: 22.7mo.
Results
2-yr OS: 82.4% vs 73.5%, arm A vs B; HR 0.67, 95%CI 0.51–0.89; P=.005.
2-yr radiographic PFS: 68.2% vs 47.5%, arm A vs B; HR 0.48, 95%CI 0.39–0.60; P<.001.
2-yr radiographic PFS: 68.2% vs 47.5%, arm A vs B; HR 0.48, 95%CI 0.39–0.60; P<.001.
Adverse events
Overall: Grade 3–4 events 42.2% vs 40.8% (arm A vs B).
Common (any grade): Hot flush 22.7% vs 16.3%; fatigue 19.7% vs 16.7%; hypertension 17.7% vs 15.6%; rash more frequent with apalutamide.
Common (any grade): Hot flush 22.7% vs 16.3%; fatigue 19.7% vs 16.7%; hypertension 17.7% vs 15.6%; rash more frequent with apalutamide.
Conclusions
Apalutamide + ADT significantly improved OS and radiographic PFS versus ADT alone across high- and low-volume metastatic castration-sensitive prostate cancer, without compromising health-related quality of life.
Key Limitations
Placebo comparator (ADT alone); small proportion received prior docetaxel, limiting conclusions about apalutamide added to chemohormonal therapy or triplet sequencing.
Clinical Context
FDA approved apalutamide for mCSPC in 2019 based on TITAN. ASCO/ESMO list apalutamide + ADT as a standard first-line option for metastatic castration-sensitive prostate cancer regardless of disease volume.
References