TABLE 1.
Characteristics of Clinical Trials Included in the Network Meta-Analyses.
| Trials | Overall pateints | Patients with DOC | Experimental arm (n) | Control arm (n) | Median age (range) (E vs C) | ECOG PS score,n(%) (E vs C) | Gleason score at initial diagnosis,n(%) (E vs C) | Metastatic volume (E vs C) | Median PSA(range), ng/ml (E vs C) | DOC initiation | Cycles of DOC | Efficacy outcomes in NMA c |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ARCHES (Armstrong et al., 2019; Azad et al., 2021) | 1150 | 205 | ADT+Docetaxel+Enzalutamide (103) | ADT+Docetaxel +Placebo (102) | 67(46–84) vs. 68(42–83) | 0: 76(73.8) vs. 76(74.5) 1: 26(25.2) vs. 26(25.5) Missing:1(1) | ≤7: 23(22.3) vs. 26(25.5) 8-10: 76(73.8) vs. 72(70.6) Missing: 8(3.9) | HV: 73(70.9) vs. 72(70.6) LV: 30(29.1) vs. 30(29.4) | 0.8(0.0-493.7) vs. 0.76(0.0-280.8) | Prior | Full 6 cycles used in 86% of patients | OS, rPFS, time to PSA progression, time to CR, time to first SSE, time to new antineoplastic therapy |
| ENZAMET a (Davis et al., 2019) | 1125 | 503 | ADT+Docetaxel +Enzalutamide (254) | ADT+Docetaxel +SNA (249) | 69.2(IQR:63.2–74.5) vs. 69.0 (IQR63.6–74.5) | 0: 405(72) vs. 405(72) 1-2: 158(28) vs. 157(28) | ≤7: 152(27) vs. 163(29) 8-10: 353(60) vs. 321(57) Missing: 76(13) vs. 78(14) | HV: 177(69.7) vs. 179(71.9) LV: 77(30.3) vs. 70(28.1) | NR | Prior (35%) and concomitant (65%) | Full 6 cycles used in 71% of patients | OS, PSA progression-free survival, Clinical Progression-Free Survival |
| TITAN a (Chi et al., 2019; Chi et al., 2021) | 1052 | 113 | ADT+Docetaxel+Apalutamide (58) | ADT+Docetaxel+Placebo (55) | 69 (45–94) vs. 68 (43–90) | 0: 328(62.5) vs. 348(66.0) 1-2: 197(37.5) vs. 179(34) | ≤7: 174(33.1) vs. 169(32.1) 8-10: 351(66.9) vs. 358(67.9) | HV: 325(61.9) vs. 335(63.6) LV: 200(38.1) vs. 192(36.4) | 5.97(0-2682) vs 4.02(0-2229) | Prior | In median, 6 cycles used | OS, rPFS |
| PEACE-1 (Fizazi et al., 2022) | 1172 | 710 | ADT+Docetaxel+Abiraterone+RT(+/-) (355) | ADT+Docetaxel +RT(+/-) (355) | 66(IQR:60-70) vs. 66(IQR:59-70) | 0: 250(70%) vs. 246(69%) 1-2: 105(30%) vs. 109(31%) | ≤7: 79(23%) vs. 71(20%) 8-10: 270(77%) vs. 276(80%) Missing: 6(2%) vs. 8(2%) | HV: 224(63) vs. 232(65) LV: 131(37) vs. 123(35) | 14(2-59) vs 12(3-60) | Concomitant | Full 6 cycles used in 100% of patients | OS, rPFS, CRPC-free survival |
| ARASENS b (Smith et al., 2022) | 1305 | 1305 | ADT+Docetaxel+Darolutamide (651) | ADT+Docetaxel +Placebo (654) | 67(41–89) vs. 67 (42–86) | 0: 466(71.6) vs. 462 (70.6) 1: 185(28.4) vs. 190(29.1) Missing: 2(1) | ≤7: 122(18.7) vs. 118(18.0) 8-10: 505(77.6) vs. 516(78.9) Missing: 24(3.7) vs. 20(3.1) | M1a: 23(3.5) vs. 16(2.4) M1b: 517(79.4) vs. 520(79.5) M1c: 111(17.1) vs. 118(18.0) | 30.3(0.0-9219.0) vs. 24.2(0.0-11947.0 | Concomitant | Full 6 cycles used in 100% of patients | OS, time to CRPC, time to first SSE, time to initiation of subsequent systemic antineoplastic therapy |
The characteristics of ENZAMET and TITAN were from overall population. Metastatic Volume in ENZAMET was from DOC population.
No high or low volume of metastasis is reported in ARASENS.
Definitions and results of efficacy outcomes in NMA are listed in Supplementary Tables S2, S3.
Abbreviations: ADT, androgen-deprivation therapy; ARASENS, ODM-201 in Addition to Standard ADT and Docetaxel in Metastatic Castration Sensitive Prostate Cancer; ARCHES, A Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC); C, Control Arm; DOC, docetaxel; ECOG PS, Eastern Cooperative Oncology Group Performance Status; E, Experimental Arm ; ENZAMET, Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate cancer; HL, high volume; LV, low volume; NR, not reported; OS, overall survival; PEACE-1, A Phase IIIStudy for Patients With Metastatic Hormone-natïve Prostate Cancer; rPFS, Radiographic progression-free survival; RT, radiotherapy; SNA, standard nonsteroidal antiandrogen (bicalutamide, nilutamide or flutamide); TITAN, Targeted Investigational Treatment Analysis of Novel Anti-androgen.