Table 1.

Recently presented or published phase III clinical trials assessing novel ARSIs in nonmetastatic castration-resistant setting.

Study [Author, Year]	Treatment	Clinical Setting	MFS Benefit	OS Benefit	Adverse Events of Any Grade
PROSPER [Hussain et al., 2018] [12,13]	Enzalutamide + ADT (vs. placebo + ADT)	nmCRPC	36.6 months vs. 14.7 months (p < 0.001)	67.0 months vs. 56.3 months (p = 0.001)	More frequently (Enza vs. placebo): -Fatigue (in 33% vs. 14%) -Hypertension (in 12% vs. 5%) -Major cardiovascular events (in 5% vs. 3%) -Mental impairment disorders (in 5% vs. 2%)
SPARTAN [Smith et al., 2018] [15,16]	Apalutamide + ADT (vs. placebo + ADT)	High-risk nmCRPC	40.5 months vs. 16.2 months (p < 0.001)	Median OS not reached in the Apa or the placebo group. 25% reduction in the risk of death (HR for Apa vs. placebo, 0.75; 95% CI 0.59–0.96; p = 0.0197) [16]	More frequently (Apa vs. placebo): -Fatigue (in 30.4% vs. 21.1%) -Hypertension (in 24.8% vs. 19.8%) -Rash (in 23.8% vs. 5.5%) -Diarrhea (in 20.3% vs. 15.1%)
ARAMIS [Fizazi et al., 2019] [17,18]	Darolutamide + ADT (vs. placebo + ADT)	High-risk nmCRPC	40.4 months vs. 18.4 months (p < 0.001)	Percentage of pts alive at 3 years: 83% vs. 77% (p = 0.003) [18]	More frequently (Daro vs. placebo): -Fatigue (in 13.2% vs. 8.3%) -Hypertension (7.8% vs. 6.5%) -Cardiac arrhythmia (7.3% vs. 4.3%) -Bone fracture (in 5.5% vs. 3.6%)

Abbreviations: ADT: androgen-deprivation therapy; nmCRPC: nonmetastatic castration-resistant prostate cancer; MFS: metastasis-free survival; OS: overall survival; Enza: enzalutamide; Apa: apalutamide; Daro: darolutamide; CI: confidence intervals; HR: hazard ratio; pts: patients; ARSIs: androgen receptor signaling inhibitors.