Table 1.
Characteristics of included trials.
| Trial | Population | Enrollment | Treatment added to ADT | mHSPC cases No. (Exp. vs. Ctrl) | Inclusion of interest | Primary endpoint | Secondary endpoint (with interest) |
Follow -up, mo |
|---|---|---|---|---|---|---|---|---|
| GETUG -AFU15 [10,37] |
France and Belgium | Oct. 2004- Dec. 2008 |
Docetaxel vs. no treatment |
385 (192 vs. 193) |
1) no previous chemotherapy; 2) previous hormone therapy in metastatic setting within the past 2 months allowed; 3) 29% with metastases after previous radical treatment; 4) 48% with HVD; 5) daily prednisone use not needed; 6) 66% received ADT combined with NSAA. |
OS | cPFS, bPFS, rPFS | 84 |
| CHAARTED[11,38] | USA | July 2006- Dec. 2012 | Docetaxel vs. no treatment |
790 (397 vs. 393) |
1) no previous chemotherapy; 2) no previous hormone therapy in metastatic setting; 3) 27% with metastases after previous radical treatment; 4) 65% with HVD; 5) daily prednisone use not needed. |
OS | cPFS, time to CRPC | 54 |
| STAMPEDE-arm C [12] [31] |
UK and Swiss | Oct.2005-Mar.2013 | Docetaxel vs. no treatment |
1086 (362 vs. 724) |
1) no previous chemotherapy; 2) 5% with metastases after previous radical treatment; 3) 56% with HVD; 4) daily prednisone use needed (5mg, bid); 5) 7% with planned SOC radiotherapy. |
OS | FFS, PFS, time to any treatment after progression |
78 |
| STAMPEDE-arm G [13,30] | Nov. 2011- Jan. 2014 |
AAP vs. no treatment | 1002 (500 vs. 502) |
1) no prior chemotherapy; 2) no previous long-term hormone therapy; 3) 5% with metastases after previous radical treatment; 4) 55% with HVD; 5) 30% with planned SOC Radiotherapy. |
OS | FFS, PFS, symptomatic SRE, adverse events, QOL, PCa-specific survival |
42 | |
| STAMPEDE-arm H [18] | Jan. 2013- Sep.2016 |
Radiotherapy vs. no treatment | 2061 (1032 vs. 1029) |
1) 18% with planned DOC chemotherapy (≤6 cycles and without disease progression); 2) 100% newly diagnosed mPCa; 3) 58% with HVD. |
OS, FFS | PFS, mPFS, prostate cancer-specific survival, and symptomatic local event-free survival | 37 | |
| LATITUDE [14,36] |
Worldwide (34 countries) |
Feb. 2013- Dec.2014 | AAP vs. placebo | 1199 (597 vs. 602) |
1) no prior chemotherapy, radiation therapy, or surgery; 2) previous hormone therapy in metastatic setting within the past 3 months allowed; 3) 100% newly diagnosed mPCa; 4) mHSPC with two of three high risk factors, 80% with HVD. |
OS, rPFS | Time to PSA progression, Time to next symptomatic SRE, Time to subsequent PCa therapy |
52 |
| ENZAMET [15] |
6 countries, maily Australian and Canada | Mar.2014-Mar.2017 | Enzalutamide vs. NSAA | 1125 (563 vs. 562) |
1) 16% with DOC chemotherapy (≤2 cycles and without disease progression) before randomization; 2) previous hormone therapy in metastatic setting within the past 3 months allowed; 3) 39% with metastases after previous radical treatment; 4) 52% with HVD; 5) 44.7% with planned early DOC used. |
OS | cPFS, adverse events | 34 |
| ARCHES [16,33,35] |
Worldwide (24 countries) |
Mar. 2016- Jan.2018 |
Enzalutamide vs. placebo | 1150 (574 vs. 576) |
1) 18% with previous chemotherapy (≤6 cycles and without disease progression); 2) no previous hormone therapy in metastatic setting; 3) 26% with metastases after previous radical treatment; 4) 63% with HVD; 5) 435(38%) had received prior AA. 5) 6.7% received concomitant antiandrogens. |
OS, rPFS | time to PSA progression, time to initiation of new antineoplastic therapy, objective response | 44.6 |
| TITAN [17,34] |
Worldwide (23 countries) |
Dec.2015- July 2017 |
Apalutamide vs. placebo | 1052 (525 vs. 527) |
1) 10.7% with previous chemotherapy (≤6 cycles and without disease progression); 2) previous hormone therapy in metastatic setting within the past 3 months allowed; 3) 16% with metastases after previous radical treatment; 4) 63% with HVD; 5) NSAA allowed before randomization. |
OS, rPFS | Time to chemotherapy, time to pain progression, time to chronic opioid use, time to SRE. | 44 |
| HORRAD [43] |
Netherlands | Nov. 2004- Sep.2014 |
Radiotherapy vs. no treatment | 432 (216 vs. 216) |
1) no previous chemotherapy; 2) 100% newly diagnosed mPCa; 3) 83% with high burden in HORRAD definition. |
OS | PSA-PFS | 47 |
| PEACE-1 (Docetaxel population) [25] |
7 European countries | Nov. 2013- Dec. 2018 |
AAP+DOC vs. DOC | 710 (355 vs. 355) |
1) 100% de novo mHSPC; 2) no previous long-term hormone therapy; 3) 64% with HVD; 4) Concomitant DOC and abiraterone use; 5) Full 6 cycles of DOC administered in 100% of patients; 6) ± radiotherapy allowed. |
rPFS; OS |
CRPC-free survival, cPFS, Prostate cancer specific survival, Toxicity | 42 |
| ARASENS [26] |
Worldwide (23 countries) |
Nov. 2016- June 2018 |
DARO+DOC vs. DOC | 1306 (651 vs. 654) |
1)100% de novo mHSPC. 2) No previous chemotherapy, 2nd AR inhibitor, immunotherapy, or radiotherapy within 2 weeks before randomization; 3) NSAA allowed but should be discontinued before randomization. |
OS | CRPC-free survival, time to pain progression, time to initiation of new antineoplastic therapy, safety | 43.7 (DARO) 42.4 (Ctrl) |
AA, antiandrogen drugs; AAP, abiraterone acetate+prednisone; ADT, androgen deprivation therapy; AR, androgen receptor; bPFS, biochemical progression free survival; cPFS, clinical progression free survival; CRPC, castration resistant prostate cancer; Ctrl, control group; DARO, darolutamide; DOC, docetaxel; Exp., experimental group; FFS, failure free survival; HVD, high volume disease in CHAARTED definition; mHSPC, metastatic hormonal-sensitive prostate cancer; mPCa, metastatic prostate cancer; mPFS, metastatic progression free survival; NSAA, non-steroidal anti-androgen; including nilutamide, flutamide or bicalutamide; OS, overall survival; QOL, quality of life; rPFS, radiographic progression free survival; SRE, skeletal related events; SOC, standard of care.