| Study | Intervention | Comparison | Selection criteria | Main outcomes | |
|---|---|---|---|---|---|
| ABIRATERONE | |||||
| COU-AA-301 2012 «Fizazi K, Scher HI, Molina A ym. Abiraterone aceta...»1 |
abiraterone + prednisone HR |
placebo + prednisone |
Previous docetaxel. ECOG 0–2. PSA or radiographic progression. |
OS: 15.8 vs. 11.2 mo. (p < 0.0001, HR: 0.74, 95% CI: 0.64–0.86; p < 0.0001). FU: 20.2 mo.rPFS: no change |
|
| COU-AA-301 2011 «de Bono JS, Logothetis CJ, Molina A ym. Abirateron...»2 |
OS: 14.8 vs. 10.9 mo. (p < 0.001 HR: 0.65; 95% CI: 0.54–0.77). FU: 12.8 mo.rPFS: 5.6 vs. 3.6 mo. |
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| Radium-223 | |||||
| ALSYMPCA 2013 «Parker C, Nilsson S, Heinrich D ym. Alpha emitter ...»3 |
radium-223 | placebo | Previous or no previous docetaxel. ECOG 0–2. Two or more symptomatic bone metastases. No visceral metastases. |
OS: 14.9 vs. 11.3 mo. (p = 0.002, HR: 0.61; 95% CI: 0.46–0.81). All secondary endpoints show a benefit over best SOC. |
|
| CABAZITAXEL | |||||
| TROPIC 2013 «Bahl A, Oudard S, Tombal B ym. Impact of cabazitax...»4 |
cabazitaxel + prednisone |
mitoxantrone + prednisone |
Previous docetaxel. ECOG 0–2. |
OS: 318/378 vs. 346/377 events (OR: 2.11; 95% CI: 1.33–3.33). FU: 25.5 months OS ≥ 2 yr 27% vs. 16% PFS: - |
|
| TROPIC 2010 «de Bono JS, Oudard S, Ozguroglu M ym. Prednisone p...»5 |
OS: 15.1 vs. 12.7 mo. (p < 0.0001, HR: 0.70; 95% CI: 0.59–0.83). FU: 12.8 mo. PFS: 2.8 vs. 1.4 mo. (p < 0.0001, HR: 0.74, 95% CI: 0.64–0.86) |
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| CARD 2019 «de Wit R, de Bono J, Sternberg CN ym. Cabazitaxel ...»6 |
Cabazitaxel (25 mg/m2 Q3W) + prednisone + G-CSF |
ARTA: abiraterone + prednisone OR enzalutamide |
Previous docetaxel. Progression ≤ 12 mo. on prior alternative ARTA (either before or after docetaxel) |
Med OS 13.6 vs. 11.0 mo. (p = 0.008, HR: 0.64, 95% CI: 0.4–0.89).rPFS 8.0 vs. 3.7 mo. (p < 0.001, HR: 0.54, 95% CI: 0.40–0.73). FU: 9.2 mo. |
|
| ENZALUTAMIDE | |||||
| AFFIRM 2012 «Scher HI, Fizazi K, Saad F ym. Increased survival ...»7 |
enzalutamide | placebo | Previous docetaxel. ECOG 0–2. |
OS: 18.4 vs. 13.6 mo. (p < 0.001, HR: 0.63; 95% CI: 0.53–0.75). FU: 14.4 mo.rPFS: 8.3 vs. 2.9 mo. (HR: 0.40; 95% CI: 0.35–0.47, p < 0.0001). |
|
| PARP inhibitor | |||||
| PROfound 2020 «de Bono J, Mateo J, Fizazi K ym. Olaparib for Meta...»8, «Hussain M, Mateo J, Fizazi K ym. Survival with Ola...»9, «de Bono, J.S., et al. Final overall survival (OS) ...»10 |
olaparib | abiraterone + prednisolone or enzalutamide; cross-over allowed at progression |
Previous ARTA, alterations in HRR mutated genes |
rPFS: 7.39 vs. 3.55 mo. (p < 0.0001, HR: 0.34; 95% CI: 0.25–0.47), conf. ORR 33.3% vs. 2.3% (OR 20.86, 95% CI: 4.18–379.18).OS: 19.1 mo vs. 14.7 mo (in pts with BRCA1/2, ATM alterations) (p = 0.0175; HR 0.69, 95% CI: 0.5–0.97). |
|
| TRITON-3 «Fizazi K, Piulats JM, Reaume MN, ym. Rucaparib or ...»13 |
rucaparib (600 mg BID) | docetaxel or abiraterone acetate or enzalutamide | EOCG 0-1 Previous one ARPI BRCA 1/ 2 or ATM alteration |
rPFS: ITT 10.2 mo vs. 6.4 mo, HR 0.61; 95% CI, 0.47 to 0.80; (P<0.001 for both comparisons) |
|
| Radioligand therapy | |||||
| VISION 2021 «Sartor O, de Bono J, Chi KN ym. Lutetium-177-PSMA-...»11 |
177Lu-PSMA-617 | 177Lu-PSMA-617 + SOC or SOC alone | Previous at least 1 ARTA and one or two taxane regimens; Mandatory: PSMA-positive gallium-68 (68Ga)–labeled PSMA-PET scan |
Imaging-based PFS: 8.7 vs. 3.4 mo (p < 0.001; HR 0.40; 99.2% CI: 0.29–0.57) OS: 15.3 vs. 11.3 mo. (p < 0.001; HR 0.62; 95% CI: 0.5–0.74) |
|
| TheraP 2021 «Hofman MS, Emmett L, Sandhu S ym. [(177)Lu]Lu-PSMA...»12 |
177Lu-PSMA-617 (8.5 GBq i.v.q 6-weekly, decreasing 0.5 GBq/cycle; up to 6 cycles) |
177Lu-PSMA-617 1:1 randomisation cabazitaxel (20 mg/m2 i.v.q 3-weekly, up to 10 cycles) |
mCRPC post docetaxel, suitable for cabaziaxel | PSA reduction of ≥ 50%: 65 vs. 37 PSA responses; 66% vs. 37% by ITT; difference 29% (95% CI: 16–42; p < 0.0001; and 66% vs. 44% by treatment received; difference 23% [9–37]; p = 0.0016). |
|
| *Only studies reporting survival outcomes as primary endpoints have been included. ARTA = androgen receptor targeting agents; CI = confidence interval; ECOG = Eastern Cooperative Oncology Group; FU = follow-up; GBq = gigabecquerel; HR = hazard ratio; Lu = lutetium; mo = months OS = overall survival; OR = odds ratio; ORR = objective response rate; PSA = prostate-specific antigen; PSMA = prostate-specific membrane antigen; (r)PFS = (radiographic) progression-free survival; SOC = standard of care; yr = year; HRR= homologous recombination repair. |
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