Table 1. Active therapies for mCRPC.

Agent		Clinical trial	Patient status	Intervention	Comparison	Primary endpoint	Outcome
ARSI
	Abiraterone	COU-AA-301 [5]	Postdocetaxel mCRPC	Abiraterone+Prednisone	Placebo+Prednisone	OS	HR, 0.65; 95% CI, 0.54–0.77; p<0.001
		COU-AA-302 [6]	Chemotherapy-naiive mCRPC	Abiraterone+Prednisone	Placebo+Prednisone	rPFS and OS	rPFS: HR, 0.53; 95% CI, 0.45–0.62; p<0.001
							OS: HR, 0.75; 95% CI, 0.61–0.93; p=0.01
	Enzalutamide	AFFIRM [7]	Postdocetaxel mCRPC	Enzalutamide	Placebo	OS	HR, 0.63; 95% CI, 0.53–0.75; p<0.001
		PREVAIL [8]	Chemotherapy-naiive mCRPC	Enzalutamide	Placebo	rPFS and OS	rPFS: HR, 0.19; 95% CI, 0.15–0.23; p<0.001
							OS: HR, 0.71; 95% CI, 0.60–0.84; p<0.001
Chemotherapy
	Docetaxel	TAX 327 [3]	mCRPC	Docetaxel+Prednisone	Mitoxantrone+Prednisone	OS	Docetaxel every 3 wk: HR, 0.76; 95% CI, 0.62–0.94; p=0.009
		SWOG 99-16 [4]	mCRPC	Docetaxel+Estramustine	Mitoxantrone+Prednisone	OS	HR, 0.80; 95% CI, 0.67–0.97; p=0.02
	Cabazitaxel	TROPIC [9]	Postdocetaxel mCRPC	Cabazitaxel+Prednisone	Mitoxantrone+Prednisone	OS	HR, 0.70; 95% CI, 0.59–0.83; p<0.0001
		CARD [12]	Postdocetaxel and post-ARSI mCRPC	Cabazitaxel+Prednisone	Other ARSI (either Abiraterone+Prednisone or Enzalutamide)	rPFS	HR, 0.54; 95% CI, 0.40–0.73; p<0.001
Immunotherapy
	Sipuleucel-T	IMPACT [13]	mCRPC without visceral metastases	Sipuleucel-T	Placebo	OS	HR, 0.78; 95% CI, 0.61–0.98; p=0.03
Bone-targeted therapy
	Radium-223	ALSYMPCA [14]	mCRPC with bone metastases	Radium-223	Placebo	OS	HR, 0.70; 95% CI, 0.58?0.83; p<0.001
Radioligand therapy
	177Lu-PSMA-617	VISION [15]	Postdocetaxel and post-ARSI mCRPC	177Lu-PSMA-617+Standard care	Standard care	rPFS, OS	rPFS: HR, 0.40; 99.2% CI, 0.29–0.57; p<0.001
							OS: HR, 0.62; 95% CI, 0.52–0.74; p<0.001
PARP inhibitor
	Olaparib2	PROfound [16]	Post-ARSI mCRPC with HRRm	Olaparib	Enzalutamide or Abiraterone	rPFS	HR, 0.34; 95% CI, 0.25–0.47; p<0.001 (cohort A)
		PROpel [17]	Previously untreated mCRPC, regardless of HRRm status	Olaparib+Abiraterone	Placebo+Abiraterone	rPFS	HR, 0.66; 95% CI, 0.54–0.81; p<0.001
AKT inhibitor
	Ipatasertib	IPATential150 [18]	Previously untreated mCRPC	Ipatasertib+Abiraterone	Placebo+Abiraterone	rPFS	HR, 0.77; 95% CI, 0.61–0.98; p=0.034; significant at α=0.04 (no significant difference in the ITT population)

ARSI: androgen receptor-signaling inhibitor, CI: confidence interval, HR: hazard ratio, HRRm: homologous recombination repair gene mutation, ITT: intention-to-treat, mCRPC: metastatic castration-resistant prostate cancer, OS: overall survival, rPFS: radiographic progression-free survival.