Lisätietoa aiheesta

Randomised controlled phase II/III - second-line/third-line trials in mCRPC

Additional information
17.12.2025
EAU guideline panel
Table 1. Randomised controlled phase II/III - second-line/third-line trials in mCRPC
StudyInterventionComparisonSelection criteriaMain outcomes
ABIRATERONE
COU-AA-301
2012 «Fizazi K, Scher HI, Molina A ym. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, place»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. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011;364:1995-2005 »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.
Radium-223
ALSYMPCA
2013 «Parker C, Nilsson S, Heinrich D ym. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369:213-23 »3 		radium-223placeboPrevious 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 cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial. A»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 plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label tri»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)
CARD
2019 «de Wit R, de Bono J, Sternberg CN ym. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med 2019;381:2506-2518 »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 with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012;367:1187-97 »7		enzalutamideplaceboPrevious 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 Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020;382:2091-2102 »8, «Hussain M, Mateo J, Fizazi K ym. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020;383:2345-2357 »9, «de Bono, J.S., et al. Final overall survival (OS) analysis of PROfound: Olaparib vs physician's choice of enzalutamide or abiraterone in patients (pts) with metastatic castration-resistant prostate ca»10		olaparibabiraterone +
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 Physician's Choice in Metastatic Prostate Cancer. N Engl J Med 2023;388(8):719-732 »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-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2021;385:1091-1103 »11		177Lu-PSMA-617177Lu-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-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet 202»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 cabaziaxelPSA 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).
PSMAfore 2023 «Fizazi K, Piulats JM, Reaume MN, ym. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med 2023;388(8):719-732 »13177Lu-PSMA-617 at a dosage of 7·4 GBq (200 mCi)1398042195±139804219510%; 6 cycles 177Lu-PSMA-617 1:1 randomisation to ARPI- change (abiraterone or enzalutamide) One previous ARPI for mCRPC
No previous taxane in CRPC or HSPCb 		First endpoint: rPFS 3rd data-cut-off : 11·60 mo (95% CI 9·30–14·19) vs 5·59 mo (4·21–5·95) (HR 0·49 [95% CI 0·39–0·61])
*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.

References

  1. Fizazi K, Scher HI, Molina A ym. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 2012;13:983-92 «PMID: 22995653»PubMed
  2. de Bono JS, Logothetis CJ, Molina A ym. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011;364:1995-2005 «PMID: 21612468»PubMed
  3. Parker C, Nilsson S, Heinrich D ym. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369:213-23 «PMID: 23863050»PubMed
  4. Bahl A, Oudard S, Tombal B ym. Impact of cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial. Ann Oncol 2013;24:2402-8 «PMID: 23723295»PubMed
  5. de Bono JS, Oudard S, Ozguroglu M ym. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010;376:1147-54 «PMID: 20888992»PubMed
  6. de Wit R, de Bono J, Sternberg CN ym. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med 2019;381:2506-2518 «PMID: 31566937»PubMed
  7. Scher HI, Fizazi K, Saad F ym. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012;367:1187-97 «PMID: 22894553»PubMed
  8. de Bono J, Mateo J, Fizazi K ym. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020;382:2091-2102 «PMID: 32343890»PubMed
  9. Hussain M, Mateo J, Fizazi K ym. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020;383:2345-2357 «PMID: 32955174»PubMed
  10. de Bono, J.S., et al. Final overall survival (OS) analysis of PROfound: Olaparib vs physician's choice of enzalutamide or abiraterone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations. Ann Oncol 2020;31:S507
  11. Sartor O, de Bono J, Chi KN ym. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2021;385:1091-1103 «PMID: 34161051»PubMed
  12. Hofman MS, Emmett L, Sandhu S ym. [(177)Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet 2021;397:797-804 «PMID: 33581798»PubMed
  13. Fizazi K, Piulats JM, Reaume MN, ym. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med 2023;388(8):719-732 «PMID: 36795891»PubMed