Table 1.

Current FDA-approved systemic therapies for mCRPC.

Mechanism of action	Drug	Specific indications or restrictions in the mCRPC setting	Key trials
ARPI	Abiraterone [7]	None	COU-AA-301 [20] COU-AA-302 [100]
	Enzalutamide [8]	None	AFFIRM [21]
Taxane chemotherapy	Docetaxel [9]	None	TAX 327 [92]
	Cabazitaxel [10]	After docetaxel	EFC6193/TROPIC [22]
Radiopharmaceutical (alpha emitter)	Radium-223 [11]	Symptomatic bone metastases with no visceral metastases	ALSYMPCA [23]
Cell-based immunotherapy	Sipuleucel-T [12]	Asymptomatic or minimally symptomatic disease	IMPACT [24]
Radiopharmaceutical (PSMA-targeted radioligand)	[177Lu]Lu-PSMA-617 [13]	PSMA-positive metastatic disease; prior treatment with ARPI and taxane	VISION [25]
PARP inhibitor	Olaparib [14]	Monotherapy: HRR-mutated; after ARPI In combination with abiraterone: BRCA-mutated	PROfound [58] PROpel [26, 60]
	Rucaparib [15]	BRCA-mutated; after ARPI and docetaxel	TRITON2 [27]
	Talazoparib [18]	In combination with enzalutamide: HRR-mutated	TALAPRO-2 [28]
	Niraparib [16]	In combination with abiraterone: BRCA-mutated	MAGNITUDE [29]
Immune checkpoint inhibitor	Pembrolizumab [17]	MSI-H, dMMR, TMB ≥ 10 mutations/megabase (tumor-agnostic)	Retrospective studies [31, 68]

ARPI androgen receptor pathway inhibitor, BRCA breast cancer gene, dMMR deficient mismatch repair, FDA Food and Drug Administration, HRR homologous recombination repair, Lu lutetium, mCRPC metastatic castration-resistant prostate cancer, MSI-H microsatellite instability-high, PARP poly (ADP-ribose) polymerase, PSMA prostate-specific membrane antigen, TMB tumor mutational burden.