Table 2.
Guideline-recommended therapies in mCRPC and their pivotal trials.
| Drug | Clinical trial name | Comparator | Study population | Results for primary endpoint(s) |
|---|---|---|---|---|
| Abiraterone | COU-AA-301 (NCT00638690) | Placebo | mCRPC with prior docetaxel |
OS, median 15.8 months (abiraterone) vs 11.2 months (placebo), HR 0.74; 95% CI 0.64–0.86; p < 0.0001 [101] |
| COU-AA-302 (NCT00887198) | Placebo | mCRPC without prior docetaxel |
OS, median 34.7 months (abiraterone) vs 30.3 months (placebo); HR 0.81; 95% CI 0.70–0.93; p = 0.003 [102] |
|
| Enzalutamide | AFFIRM (NCT00974311) | Placebo | mCRPC with prior docetaxel |
OS, median 18.4 months (enzalutamide) vs 13.6 months (placebo); HR 0.63; 95% CI 0.53–0.75; p < 0.001 [21] |
| PREVAIL (NCT01212991) | Placebo | mCRPC without prior docetaxel |
OS, median 32.4 months (enzalutamide) vs 30.2 months (placebo); HR 0.71; 95% CI 0.60–0.84; p < 0.0001 [103] |
|
| Docetaxel | TAX 327 (NCT00675545) | Mitoxantrone | mCRPC |
OS, median 19.2 months (docetaxel) vs 16.3 months (mitoxantrone); HR 0.79; 95% CI 0.67–0.93; p = 0.004 [92] |
| Cabazitaxel | TROPIC (NCT00417079) | Mitoxantrone | mCRPC with prior docetaxel |
OS, 15.1 months (cabazitaxel) vs 12.7 months (mitoxantrone); HR 0.70; 95% CI 0.59–0.83; p < 0.001 [22] |
| CARD (NCT02485691) | ARPI (abiraterone or enzalutamide) | mCRPC with prior ARPI and docetaxel |
OS, 13.6 months (cabazitaxel) vs 11.0 months (ARPI); HR 0.64; 95% CI 0.46–0.89; p = 0.008 [104] |
|
| Radium-223 | ALSYMPCA (NCT00699751) | Placebo | mCRPC with ≥2 bone metastases and no visceral metastases; received prior docetaxel if able |
OS, median 14.0 months (radium-223) vs 11.2 months (placebo); HR 0.70; 95% CI 0.55–0.88; p < 0.001 [23] |
| Sipuleucel-T | IMPACT (NCT00065442) | Placebo | Asymptomatic or minimally symptomatic mCRPC with no visceral metastases |
OS, median 25.8 months (sipuleucel-T) vs 21.7 months (placebo); HR 0.78; 95% CI 0.61–0.98; p = 0.03 [24] |
| [177Lu]Lu-PSMA-617 (plus BSOCa) | VISION (NCT03511664) | Best SOC alone, including, second ARPI or glucocorticoids | PSMA-positive mCRPC with ≥1 prior ARPI and ≥1 taxane |
Imaging-based PFS, median 8.7 months ([177Lu]Lu-PSMA-617) vs 3.4 months (BSOC); HR 0.40; 95% CI 0.29–0.57; p < 0.001 [25] OS, median 15.3 months ([177Lu]Lu-PSMA-617) vs 11.3 months (BSOC); HR 0.62; 95% CI 0.52–0.74; p < 0.001 [25] |
| PSMAfore (NCT04689828) | Change of ARPI, plus best SOC | PSMA-positive mCRPC with progression after 1 prior ARPI and no prior taxane in the CRPC or mHSPC settings |
Imaging-based PFS, median 12.0 months ([177Lu]Lu-PSMA-617) vs 5.6 months (ARPI); HR 0.41; 95% CI 0.29–0.56; p < 0.001 [81, 82] |
|
| Olaparib (monotherapy or in combination with abiraterone) | PROfound (NCT02987543) | Second ARPI (abiraterone or enzalutamide) | mCRPC that is HRR-deficient; prior ARPI ± prior taxane |
Imaging-based PFS (in cohort with BRCA1, BRCA2, or ATM alteration): median 7.4 months (olaparib) vs 3.6 months (ARPI); HR 0.34; 95% CI 0.25–0.47; p < 0.001 [58] |
| PROpel (NCT03732820) | Placebo (with abiraterone) | mCRPC unselected by HRR status |
ITT group: Imaging-based PFS: median 24.8 months (olaparib + abiraterone) vs 16.6 months (abiraterone); HR 0.66; 95% CI 0.54–0.81; p < 0.001 [60] OS: median 42.1 months (olaparib + abiraterone) vs 34.7 months (abiraterone); HR 0.81; 95% CI 0.67–1.00; p = 0.054 [26] HRR+ group: Imaging-based PFS: HR 0.50; 95% CI 0.34–0.73 OS: HR 0.66; 95% CI 0.45–0.95 [26] BRCA subgroup: Imaging-based PFS: HR 0.23; 95% CI 0.12–0.43 OS: HR 0.29; 95% CI 0.14–0.56 [26] |
|
| Rucaparib | TRITON-3 (NCT02975934) | Physician’s choice (abiraterone, enzalutamide or docetaxel) | mCRPC that is HRR-deficient (BRCA1/2 or ATM alteration only) with prior ARPI |
Imaging-based PFS, BRCA subgroup: median 11.2 months (rucaparib) vs 6.4 months (physician’s choice); HR 0.50; 95% CI 0.36–0.69 [57] ITT group: median 10.2 months (rucaparib) vs 6.4 months (physician’s choice); HR 0.61; 95% CI 0.47–0.80; p < 0.001 for both comparisons [57] |
| Talazoparib (in combination with enzalutamide) | TALAPRO-2 (NCT03395197) | Placebo (with enzalutamide) | mCRPC with genetic alterations to HRR genes |
Imaging-based PFS: ITT group: median not reached (talazoparib + enzalutamide) vs 21.9 months (enzalutamide); HR 0.63; 95% CI 0.51–0.78; p < 0.001 [28] HRR+ group: HR 0.45; 95% CI 0.33–0.61 [105] BRCA subgroup: HR 0.20; 95% CI 0.11–0.36 [105] |
| Niraparib (in combination with abiraterone) | MAGNITUDE | Placebo (with abiraterone) | mCRPC with genetic alterations to HRR genes |
Imaging-based PFS, BRCA subgroup: median 16.6 months (niraparib + abiraterone) vs 10.9 months (abiraterone); HR 0.53; 95% CI 0.36–0.79; p = 0.001 [29] Overall HRR+ group, median 16.5 months (niraparib + abiraterone) vs 13.7 months (abiraterone); HR 0.73; 95% CI 0.56–0.96; p = 0.022 [29] |
| Pembrolizumab | Data pooled from five clinical trials | No comparator | Any advanced solid tumor that is MSI-H OR dMMR with no satisfactory alternative treatment options |
ORR 39.6%; 95% CI 31.7–47.9% [69] |
ARPI androgen receptor pathway inhibitor, ATM ataxia–telangiectasia mutated, BRCA breast cancer gene, BSOC best standard of care, CRPC castration-resistant prostate cancer, dMMR deficient mismatch repair, HRR homologous recombination repair, HHR+ homologous recombination repair positive, ITT intention-to-treat, Lu lutetium, mCRPC metastatic castration-resistant prostate cancer, mHSPC metastatic hormone-sensitive prostate cancer, MSI-H microsatellite instability-high, OR objective response, ORR objective response rate, OS overall survival, PFS progression-free survival, PSMA prostate-specific membrane antigen.
aBSOC could include an ARPI in VISION but not in PSMAfore.