Background
Methods
Study population
NCT identifier
|
Trial title
|
Phase
|
Reference
|
---|---|---|---|
NCT01946204 | A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Study of ARN-509 in Men With Non-Metastatic (M0) Castration-Resistant Prostate Cancer | Phase III | Apalutamide versus placebo |
NCT00744497 | A Randomized Double-Blind Phase 3 Trial Comparing Docetaxel Combined With Dasatinib to Docetaxel Combined With Placebo in Castration-Resistant Prostate Cancer | Phase III | Dasatinib, docetaxel, prednisone versus placebo, docetaxel, prednisone |
NCT02057666 | A Phase III, Randomised, Double-Blind, Placebo-Controlled Study Of Tasquinimod In Asian Chemo-Naïve Patients With Metastatic Castrate-Resistant Prostate Cancer | Phase III | Tasquinimod versus placebo |
NCT01234311 | A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Tasquinimod in Men With Metastatic Castrate Resistant Prostate Cancer | Phase III | Tasquinimod versus placebo |
NCT01188187 | A Randomized Phase 3 Study Comparing Standard First-Line Docetaxel/Prednisone to Docetaxel/Prednisone in Combination With Custirsen (OGX-011) in Men With Metastatic Castrate Resistant Prostate Cancer | Phase III | Custirsen, docetaxel, prednisone versus docetaxel, prednisone |
NCT02023697 | A Three Arm Randomized, Open-label Phase II Study of Radium-223 Dichloride 50 kBq/kg (55 kBq/kg After Implementation of NIST Update) Versus 80 kBq/kg (88 kBq/kg After Implementation of NIST Update), and Versus 50 kBq/kg (55 kBq/kg After Implementation of NIST Update) in an Extended Dosing Schedule in Subjects With Castration-resistant Prostate Cancer Metastatic to the Bone | Phase II | Radium-223 dichloride standard versus high versus extended standard doses |
NCT01212991 | Prevail: A Multinational Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy And Safety Study Of Oral Mdv3100 In Chemotherapy-naïve Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy | Phase III | Enzalutamide versus placebo |
NCT01685983 | A Phase 2 Open Label Study of Abiraterone Acetate (JNJ-212082) and Prednisolone in Patients With Advanced Prostate Cancer Who Have Failed Androgen Deprivation and Docetaxel-Based Chemotherapy | Phase II | Abiraterone versus prednisolone |
NCT02003924 | Prosper: A Multinational, Phase 3, Randomized, Double-blind, Placebo-controlled, Efficacy And Safety Study Of Enzalutamide In Patients With Nonmetastatic Castration-resistant Prostate Cancer | Phase III | Enzalutamide versus placebo |
NCT01977651 | A Multicenter, Single-Arm, Open-Label, Post-Marketing Safety Study to Evaluate the Risk of Seizure Among Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated With Enzalutamide Who Are at Potential Increased Risk of Seizure | Phase IV | Enzalutamide |
NCT02987543 | A Phase III, Open Label, Randomized Study to Assess the Efficacy and Safety of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have Homologous Recombination Repair Gene Mutations (PROfound) | Phase III | Olaparib versus enzalutamide or abiraterone acetate |
NCT01188187 | A Randomized Phase 3 Study Comparing Standard First-Line Docetaxel/Prednisone to Docetaxel/Prednisone in Combination With Custirsen (OGX-011) in Men With Metastatic Castrate Resistant Prostate Cancer | Phase III | Custirsen, docetaxel, prednisone versus docetaxel, prednisone |
NCT02200614 | A Multinational, Randomised, Double-blind, Placebo-controlled, Phase III Efficacy and Safety Study of BAY1841788 (ODM-201) in Men With High-risk Non-metastatic Castration-resistant Prostate Cancer | Phase III | BAY1841788 (ODM-201) versus placebo |
NCT02257736 | A Phase 3 Randomized, Placebo-controlled Double-blind Study of JNJ-56021927 in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Subjects With Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC) | Phase III | Apalutamide, abiraterone acetate, prednisone versus abiraterone acetate, prednisone |
NCT00626548 | A Phase III, Randomised, Placebo-controlled, Double-blind Study to Assess the Efficacy and Safety of Once-daily Orally Administered ZD4054 (Zibotentan) 10 mg in Non-metastatic Hormone-resistant Prostate Cancer Patients | Phase III | Zibotentan versus placebo |
NCT00554229 | A Phase III Trial to Test the Efficacy of ZD4054(Zibotentan), an Endothelin A Receptor Antagonist, Versus Placebo in Patients With Hormone Resistant Prostate Cancer (HRPC) and Bone Metastasis Who Are Pain Free and Mildly Symptomatic | Phase III | Zibotentan versus placebo |
NCT02677896 | A Multinational, Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC) | Phase III | Enzalutamide, androgen deprivation therapy versus placebo, androgen deprivation therapy |
NCT01217697 | An Open Label Study of Abiraterone Acetate in Subjects With Metastatic Castration-Resistant Prostate Cancer Who Have Progressed After Taxane-Based Chemotherapy | EAP | Abiraterone acetate versus prednisone |
Data collection and definitions
Statistical analysis
Results
Baseline characteristics
Overall (n = 299) | Clinical trial | |||
---|---|---|---|---|
Participants (n = 65) | Non-participants (n = 234) |
p
| ||
Age | 66.5 (61.0–71.8) | 65.0 (62.0–71.0) | 67.0 (61.0–72.0) | 0.384 |
Body mass index | 23.1 (20.9–24.7) | 22.9 (21.3–24.7) | 23.4 (21.2–25.1) | 0.345 |
Laboratory valuesa | ||||
PSA (ng/mL) | 69.2 (15.0–182.0) | 25.8 (9.6–73.6) | 88.4 (18.0–247.3) | 0.005 |
Hemoglobin (g/dL) | 12.0 (10.7–13.0) | 12.4 (11.7–13.3) | 11.9 (10.4–12.9) | 0.514 |
Albumin (U/L) | 4.0 (3.7–4.4) | 4.3 (4.0–4.5) | 4.0 (3.7–4.3) | 0.001 |
ALP (U/L) | 109.0 (70.0–209.0) | 88.0 (67.0–133.5) | 118 (71.0–221.5) | 0.070 |
WBC count (× 109/L) | 5.8 (4.8–7.3) | 5.8 (4.7–7.3) | 5.8 (4.9–7.3) | 0.919 |
T stage | 0.764 | |||
≤ T2 | 187 (62.5%) | 42 (64.7%) | 145 (61.9%) | |
≥ T3 | 112 (37.5%) | 23 (35.3%) | 89 (38.1%) | |
N stage | 0.491 | |||
N0 | 127 (42.5%) | 30 (46.2%) | 97 (41.5%) | |
N1 | 172 (57.5%) | 35 (53.8%) | 137 (58.5%) | |
M stage | 1.000 | |||
M0 | 73 (24.4%) | 15 (23.1%) | 58 (24.8%) | |
M1 | 226 (75.6%) | 50 (76.9%) | 176 (75.2%) | |
Metastatic site | ||||
Bone | 166 (55.5%) | 37 (57.0%) | 129 (55.1%) | 0.856 |
Visceral | 8 (2.7%) | 8 (12.3%) | 0 (0.0%) | 0.215 |
Lymph node | 142 (47.5%) | 26 (40.0%) | 116 (49.6%) | 0.116 |
Gleason score | 0.267 | |||
≤ 7 | 156 (52.2%) | 30 (46.2%) | 126 (53.8%) | |
≥ 8 | 143 (47.8%) | 35 (53.8%) | 108 (46.2%) | |
CCI | 0.780 | |||
≤ 1 | 142 (%) | 32 (49.2%) | 110 (47.0%) | |
≥ 2 | 157 (%) | 33 (50.8%) | 124 (53.0%) | |
ECOG PS | 0.033 | |||
≤ 1 | 261 (87.3%) | 62 (95.4%) | 199 (85.1%) | |
≥ 2 | 38 (12.7%) | 3 (4.6%) | 35 (14.9%) | |
Primary treatmentb | ||||
Prostatectomy | 149 (49.8%) | 47 (72.3%) | 102 (43.6%) | < 0.001 |
Radiation therapy | 33 (11.0%) | 10 (15.4%) | 23 (9.8%) | 0.261 |
Overall (n = 299) | Clinical trial | |||
---|---|---|---|---|
Participants (n = 65) | Non-participants (n = 234) |
p
| ||
Docetaxel | ||||
N | 242 (80.9%) | 41 (63.1%) | 201 (85.9%) | 0.001 |
No. cycles | 4.0 (2.0–9.0) | 7.0 (4.0–12.5) | 4.0 (2.0–9.0) | 0.003 |
ARAT agent use | ||||
Pre-chemotherapy | 0.502 | |||
Abiraterone | 10 (3.3%) | 2 (3.1%) | 8 (3.4%) | |
Enzalutamide | 15 (5.0%) | 4 (6.2%) | 11 (4.7%) | |
Post-chemotherapy | < 0.001 | |||
Abiraterone | 23 (7.7%) | 13 (20.0%) | 10 (4.3%) | |
Enzalutamide | 108 (36.1%) | 9 (13.8%) | 99 (42.3%) | |
Cabazitaxel | 1 (0.3%) | 0 (0.0%) | 1 (0.4%) | 1.000 |
Radium-223 | 5 (1.7%) | 3 (4.6%) | 2 (0.9%) | 0.070 |
Survival outcome according to clinical trial participation
Overall (n = 299) | Clinical trial | |||
---|---|---|---|---|
Participants (n = 65) | Non-participants (n = 234) |
p
| ||
No. cancer-specific deaths | 187 (62.5%) | 44 (67.7%) | 143 (61.1%) | 0.364 |
2-year cancer-specific survival | 46.8% | 61.3% | 42.4% | 0.003 |
CRPC to death (months) | 13.0 (6.0–24.3) | 23.5 (13.3–30.5) | 11.0 (5.0–19.3) | < 0.001 |
Total follow-up (months) | 16.0 (7.2–26.0) | 26.0 (16.0–39.8) | 13.5 (6.0–24.0) | < 0.001 |
Predictors of cancer-specific survival
Univariate | Multivariate | |||||
---|---|---|---|---|---|---|
HR | (95% CI) |
P
| HR | (95% CI) |
p
| |
Age | 1.038 | (1.016–1.061) | 0.001 | 1.020 | (0.998–1.042) | 0.069 |
Body mass index | 0.968 | (0.901–1.041) | 0.382 | |||
PSAa | 1.001 | (1.000-1.001) | < 0.001 | 1.001 | (1.000–1.001) | 0.018 |
Hemoglobina | 1.001 | (0.999-1.002) | 0.306 | |||
Albumina | 0.408 | (0.301-0.553) | < 0.001 | |||
Alkaline phosphatasea | 1.001 | (1.000–1.001) | < 0.001 | 1.001 | (1.001–1.002) | < 0.001 |
T stage (≥T3 vs. ≤T2) | 0.865 | (0.524–1.430) | 0.271 | |||
N stage (1 vs. 0) | 1.251 | (0.922–1.697) | 0.152 | |||
M stage (1 vs. 0) | 1.528 | (0.983–2.376) | 0.062 | |||
Gleason score (≥8 vs. ≤7) | 1.957 | (1.441–2.658) | < 0.001 | 2.004 | (1.452–2.767) | < 0.001 |
CCI ≥4 | 1.197 | (0.811–1.765) | 0.365 | |||
ECOG ≥2 | 1.802 | (1.216–2.670) | 0.003 | 1.304 | (1.164–2.158) | 0.035 |
Docetaxel cycles | 0.926 | (0.900–0.953) | 0.026 | 0.943 | (0.915–0.972) | 0.011 |
Primary treatment | ||||||
Prostatectomy | 1 | (reference) | ||||
Radiation therapy | 0.778 | (0.580–1.141) | 0.584 | |||
ARAT agent sequencing | ||||||
Pre-chemotherapy | 1 | (reference) | ||||
Post-chemotherapy | 0.865 | (0.524–1.430) | 0.572 | |||
Radium-223 administration | 0.803 | (0.255–2.527) | 0.707 | |||
Clinical trial participation | 0.593 | (0.417–0.843) | 0.004 | 0.585 | (0.429–0.797) | 0.038 |