Trial	Intervention	Primary endpoint	Outcomes	Implications for practice
Metastatic hormone‐sensitive prostate cancer
Docetaxel
STAMPEDE (Arm C) (2016) 65	ADT ± docetaxel	OS	Median OS 43.1 (ADT) v 59.1 (ADT + docetaxel) months (including M1 cohort only) (HR, 0.81) Median OS: low volume* (HR, 0.76) v high volume † (HR, 0.81)	Docetaxel is subsidised on the PBS; it should be considered in all fit patients with mHSPC, particularly with high volume disease
CHAARTED (2015) 66	ADT ± docetaxel	OS	Median OS 47.2 (ADT) v 57.6 (ADT + docetaxel) months (HR, 0.72) Median OS: low volume (HR, 1.04) v high volume (HR, 0.63)
Enzalutamide
ENZAMET (2019) 67	ADT ± enzalutamide v ADT + non‐steroidal anti‐androgen therapy (45% concurrent docetaxel)	OS	Rates of OS at 3 years: 72% (ADT + non‐steroidal AAT) v 80% (ADT+ enzalutamide) (HR, 0.67)	Not currently subsidised on the PBS for this indication; patients can choose to self‐fund enzalutamide
ARCHES (2019) 68	ADT ± enzalutamide (18% had prior docetaxel)	rPFS	Median OS not reached in either group (HR, 0.66) rPFS (HR, 0.39)
Abiraterone
LATITUDE (2017) 69	ADT ± abiraterone	OS, rPFS	Median OS 36.5 (ADT) v 53.3 (ADT + abiraterone) months (HR, 0.66) Median rPFS 14.8 (ADT) v 33.0 months (ADT + abiraterone) (HR, 0.47)	Not currently subsidised on the PBS for this indication; patients can choose to self‐fund abiraterone
STAMPEDE (Arm G) (2017) 70	ADT ± abiraterone	OS	Median OS 3.8 (ADT) v 6.6 year (ADT + abiraterone) (HR,0.60) Median OS: low volume (HR, 0.54) v high volume (HR, 0.59)
PEACE‐1 (2021) 71	ADT ± docetaxel v ADT + abiraterone ± docetaxel (± local RT)	PFS, OS	Median OS (ADT + docetaxel alone) v NR (ADT + docetaxel + abiraterone) (HR; 0.82) rPFS (HR, 0.50)
Apalutamide
TITAN (2019) 72	ADT ± apalutamide (11% had prior docetaxel)	PFS, OS	Median OS 52.2 months (ADT) v NR (ADT + apalutamide) (HR, 0.65) rPFS at 24 months: 46.5% (ADT) v 68.2% (ADT + apalutamide) (HR, 0.48)	Not currently subsidised on the PBS for this indication
Darolutamide
ARASENS (2022) 73	ADT + docetaxel ± darolutamide	OS	Median OS 48.9 (ADT + docetaxel) months v NR (ADT + docetaxel + darolutamide) (HR, 0.68)	Not currently subsidised on the PBS for this indication
Radiotherapy to the prostate
STAMPEDE (Arm H) (2018) 74	ADT ± radiotherapy to the prostate	OS	Radiotherapy improved failure‐free survival (HR, 0.76) but not OS (HR, 0.92) Survival at 3 years: Low volume: 73% (no RT) v 81% (RT) High volume: 54% (no RT) v 53% (RT) Failure‐free survival at 3 years: Low volume: 33% (no RT) v 50% (RT) High volume: 17 (no RT) v 18% (RT)	Radiotherapy to the prostate recommended in patients with recently diagnosed metastatic low volume prostate cancer
Non‐metastatic castration‐resistant prostate cancer
Enzalutamide
PROSPER (2020) 75	ADT ± enzalutamide	OS	Median OS 56.3 (ADT) v 67.0 (ADT + enzalutamide) months (HR, 0.73)	Not currently subsidised on the PBS for this indication
Apalutamide
SPARTAN (2018) 76	ADT ± apalutamide	Metastasis‐free survival	Metastasis‐free survival was 16.2 (ADT) v 40.5 (ADT + apalutamide) months (HR, 0.28) Median O 59.9 (ADT) v 73.9 (ADT + apalutamide) months (HR, 0.78)	Apalutamide is available on the PBS for this indication
Darolutamide
ARAMIS (2019) 77	ADT ± darolutamide	Metastasis‐free survival	Metastasis‐free survival was 18.4 (ADT) v 40.4 (ADT + darolutamide) months (HR, 0.41) OS at 3 years: 77% (ADT) v 83% (ADT + darolutamide) (HR, 0.69)	Darolutamide is available on the PBS for this indication
Metastatic castration‐resistant prostate cancer
Cabazitaxel
TROPIC (2010) 78	Cabazitaxel 25mg/m 2 v 12mg/m 2 mitoxantrone	OS	Median OS: 12.7 (mitoxantrone) v 15.1 (cabazitaxel) months (HR, 0.70)	Cabazitaxel is used after a patient has progressed on docetaxel and is PBS‐subsidised for this indication
Abiraterone
COU‐AA‐301 (2011) 79	ADT ± abiraterone (post docetaxel)	OS	Median OS 10.9 (ADT) v 14.8 (ADT + abiraterone) months (HR, 0.65)	Abiraterone is available on the PBS for this indication; it can be used before or after chemotherapy
COU‐AA‐302 (2013) 80	ADT ± abiraterone (pre docetaxel)	OS, rPFS	Median rPFS 8.3 (ADT) v 16.5 (ADT + abiraterone) months (HR, 0.53) Median OS 30.3 (ADT) v 34.7 (ADT + abiraterone) months (HR, 0.81)
Enzalutamide
PREVAIL (2014) 81	ADT ± enzalutamide (pre docetaxel)	OS, rPFS	Median rPFS 5.4 (ADT) v 20.0 months (ADT + enzalutamide) (HR, 0.32) Median OS 31 (ADT) v 36 (ADT + enzalutamide) months (HR, 0.83)	Enzalutamide is available on the PBS for this indication; it can be used before or after chemotherapy
AFFIRM (2012) 82	ADT ± enzalutamide (post docetaxel)	OS	OS 13.8 (ADT) v 18.4 (ADT + enzalutamide) months (HR, 0.63)
Olaparib
PROFound (2020) 83	Olaparib v abiraterone/enzalutamide (in HRD+ patients only)	rPFS	Cohort A (patients with a BRCA1, BRCA2, or ATM mutation): median rPFS 3.6 (control) v 7.4 months (olaparib) (HR, 0.34) Overall cohort: Median rPFS 3.5 (control) v 5.8 (olaparib) months (HR, 0.49) Median OS (cohort A): 14.7 (control) v 19.1 (olaparib) months (HR, 0.69)	Approved on the PBS for use in mCRPC in patients with a BRCA1 or BRCA2 mutation and who have progressed on a prior anti‐androgen
LuPSMA
TheraP (2021) 84	177Lu‐PSMA v cabazitaxel	PSA response rate	PSA response 37% (cabazitaxel) v 66% (177Lu‐PSMA) (P = 0.0001)	177Lu‐PSMA‐617 FDA‐approved for use after a taxane and anti‐androgen; not yet TGA‐approved; available in some centres on compassionate access and through clinical trials
VISION (2021) 85	SOC ± 177Lu‐PSMA	OS, rPFS	Median OS 11.3 (SOC) v 15.3 (SOC + 177Lu‐PSMA) months (HR, 0.62) Median rPFS 3.4 (SOC) v 8.7 months (SOC + 177Lu‐PSMA) (HR, 0.40)

AAT = α‐1 antitrypsin; ADT = androgen deprivation therapy; BSC = best standard of care; FDA = Food and Drug Administration; HR = hazard ratio; HRD + = homologous recombination deficiency; mCRPC = metastatic castration‐resistant prostate cancer; mHSPC = metastatic hormone‐sensitive; NR = not reached; OS = overall survival; PBS = Pharmaceutical Benefits Scheme; PFS = progression‐free survival; PSA = prostate‐specific antigen; rPFS = radiographic progression‐free survival; RT = radiotherapy; SOC = standard of care; TGA = Therapeutic Goods Administration.

^*Low volume (CHAARTED): less than four bone metastases.

^†High volume (CHAARTED): more than four bone metastases (at least one outside the spine or pelvis) ± visceral metastasis.