TABLE 1.
Characteristics of the included studies.
| ARSi combined with DOC + ADT | ARSi sequential to DOC + ADT | ||||
|---|---|---|---|---|---|
| Trial | ARASENS (N = 1305) | PEACE-1 (N = 710)a
(Total pts: 1172) |
ENZAMET (N = 503)a
(Total pts: 1125) |
ARCHES (N = 205)a
(Total pts: 1150) |
TITAN (N = 113)a
(Total pts: 1052) |
| First author | Smith MR | Fizazi K | Davis ID | Armstrong AJ | Chi KN |
| Year | 2022 | 2022 | 2019 | 2019 | 2019 |
| Experimental arm | Darolutamide + DOC + ADT | Abiraterone + DOC + ADT |
Enzalutamide + DOC + ADT |
Enzalutamide + DOC + ADT |
Apalutamide + DOC + ADT |
| Control arm | DOC + ADT | DOC + ADT | DOC + ADT | DOC + ADT | DOC + ADT |
| The use of docetaxel | Six cycles of docetaxel were administered concurrently with ARSI after randomization | Six cycles of docetaxel were administered concurrently with ARSI. The first docetaxel cycle had to be administered within 14 days after randomisation | Docetaxel for a maximum of 6 cycles up to 2 cycles were permitted before randomization |
Up to 6 cycles, with the last dose ≤2 months prior to randomization and with no evidence of progression during treatment or before randomization | Up to 6 cycles, with the last dose ≤2 months prior to randomization and with no evidence of progression during treatment or before randomization |
| Patients no. (Exp. vs Ctrl.) | 651/654 | 355/355 | 254/249 | 103/102 | 58/55 |
| Age, years (Exp.) | 67 (range: 41–89) | 67 (range: 37–94) | 69.2 (IQR: 63.2–74.5) | 67 (range: 46–84) | 69 (range:45–94) |
| Age, years (Ctrl.) | 67 (range: 42–86) | 66 (range: 43–87) | 69.0 (IQR: 63.6–74.5) | 68 (range: 42–83) | 68 (range:43–90) |
| Serum PSA level - ng/ml (Exp.) | Median (Range) 30.3 (0.0–9219.0) |
Median (IQR) 14 (2–59) |
NR | Median (Range) 0.8 (0.0–493.7) |
Median (Range) 5.97 (0–2682)b |
| Serum PSA level - ng/ml (Ctrl.) | Median (Range) 24.2 (0.0–11,947.0) |
Median (IQR) 12 (3–60) |
NR | Median (Range) 0.76 (0.0–280.8) |
Median (Range) 4.02 (0–2229)b |
| Gleason score at initial diagnosis -no. (%)(Exp.) |
<8:122 (18.7) ≥8:505 (77.6) |
<8:79 (23%) ≥8:270 (77%) |
<8:27%b
≥8:59.5%b |
<8:23 (22.3%) ≥8:76 (73.8%) |
<8:33.1%b
≥8:66.9%b |
| Gleason score at initial diagnosis -no. (%)(Ctrl.) |
<8:118 (18.0) ≥8:516 (78.9) |
<8:71 (20%) ≥8:276 (80%) |
<8:29%b
≥8:57.1%b |
<8:26 (25.5%) ≥8:72 (70.6%) |
<8:32.1%b
≥8:67.9%b |
| Metastasis stage at initial diagnosis -no. (%) (Exp.) |
M1: 558 (85.7) M0: 86 (13.2) |
M1: 100% | M1: 57.7%b
M0: 42.3%b |
M1: 88 (88%) M0: 12 (12%) |
M1: 78.3%b
M0: 16.2%b |
| Metastasis stage at initial diagnosis -no. (%) (Ctrl.) |
M1: 566 (86.5) M0: 82 (12.5) |
M1: 100% | M1: 58.2%b
M0: 41.8%b |
M1: 85 (83.3%) M0: 17 (16.7%) |
M1: 83.7%b
M0: 11.2%b |
| HVD vs LVD no. (Exp.) | 497/154 | 224/131 | 177/77 | 73/30 | NR |
| HVD vs LVD no. (Ctrl.) | 508/146 | 232/123 | 179/70 | 72/30 | NR |
| Completion of six docetaxel cycles (Exp. vs Ctrl.) | 87.6% vs 85.5% | median 6 cycles in both arms (IQR 6–6) | 65.4% vs 76.1% | 86.4% vs 89.2% | median 6 cycles in both arms |
| HR for OS (95% CI) | |||||
| All patients | 0.68 (0.57–0.80) | 0.75 (0.59–0.95) | 0.90 (0.62–1.31) | 0.74 (0.46–1.20) | 1.12 (0.59–2.12) |
| HVD | 0.69 (0.57–0.82) | 0.72 (0.55–0.95) | 0.97 (0.64–1.46) | NR | NR |
| LVD | 0.68 (0.41–1.13) | 0.83 (0.50–1.39) | 0.65 (0.25–1.71) | NR | NR |
| HR for rPFS✝ (95% CI) | |||||
| All patients | NR | 0.50 (0.34–0.71) | 0.48 (0.37–0.62) | 0.52 (0.30–0.89) | NR |
| HVD | NR | 0.47 (0.30–0.72) | 0.51 (0.38–0.69) | NR | NR |
| LVD | NR | 0.58 (0.29–1.15) | 0.37 (0.20–0.67) | NR | NR |
aSubgroup of patients who received docetaxel chemotherapy.✝clinical Progression-free survival (cPFS) in ENZAMET, study; ARSI: androgen receptor signaling inhibitors; ADT: androgen deprivation treatment; DOC: docetaxel; Exp.: experimental arm; Ctrl.: control arm; OS: overall survival; rPFS: radiographic progression-free survival; IQR: interquartile range; NR: not reported; HVD: patients with high volume disease; LVD: patients with low volume disease.
bData from all patients in the trial, not only those with docetaxel use.