Table 2.
Efficacy outcomes of phase 3 trials evaluating NHTs (Asian sub-analyses and the landmark studies)
| Agent | Disease phase | Asian study population (n) | Primary endpoint(s) | Outcomes (Asian study) | Outcomes (Landmark study) |
|---|---|---|---|---|---|
| Abiraterone acetate | mCNPC | LATITUDEa Japanese subgroup analysis (n = 70) [36, 37] | OS, rPFS |
Median follow-up time: 56.6 months (range 2.5–64.2) Median OS NR Overall 5-year survival rate: 69.2% (AAP) versus 53.7% (placebo) Median rPFS: NR (AAP) versus 22 months (placebo) (HR 0.219; 95% CI 0.086–0.560) |
Median follow-up time: 51.8 months (interquartile range 47.15–57.03) Median OS: 53.3 months (95% CI 48.2–NR) (AAP) versus 36.5 (95% CI 33.5–40.0) months (placebo) (HR 0.66; 95% CI 0.56–0.78; p < 0.0001) [5] Median rPFS was 33 months (AAP) versus 14.8 months (placebo); (HR 0.47; 95% CI 0.39–0.55; p < 0.001) [5] |
| Enzalutamide | mCNPC | ARCHESb Japanese subgroup analysis (n = 92) [38] | rPFS |
Median follow-up time: 15.7 months (enzalutamide) versus 15.5 months (placebo) Risk of radiographic progression or death reduced by 61% versus placebo (HR 0.39; 95% CI 0.13–1.18) |
Median follow-up time: 44.6 months Survival extended versus placebo (HR 0.66; 95% CI 0.53–0.81; p < 0.0001) [8] |
| nmCRPC | PROSPERc subgroup analysis by region (Asia vs. North America) [39] | OS |
Median follow-up time: Not reported OS benefit similar across Asia and North America (HR 1.164 [95% CI 0.824, 1.644; p = 0.3883]) |
Median follow-up time: ~ 48 months Median OS: 67.0 months (95% CI 64.0-NR) (enzalutamide) versus 56.3 months (95% CI 54.4–63.0) (placebo) [10] |
|
| mCRPC | PREVAILd Asian subpopulation (Japan, Korea, and Singapore) (n = 148) [40] | rPFS, OS |
Median follow-up time: Not reported rPFS HR 0.38 (95% CI 0.10–1.44) OS HR 0.59 (95% CI 0.29–1.23) OS not reached |
Median follow-up time: 69 months Median OS: 36 months (95% CI 34–38) (enzalutamide) versus 31 months (95% CI 29–34) (placebo) [11] |
|
| Apalutamide | mCNPC | TITANe Japanese subgroup analysis (n = 51) [42] | OS, rPFS |
Median follow-up time for OS: 25.72 months (range 5.8–31.4) OS: HR 0.840 (95% CI 0.210–3.361; p = 0.805) Median follow-up time for rPFS: 22.05 months (range 1.1–29.3) rPFS: HR 0.712 (95% CI 0.205–2.466; p = 0.59) |
Median follow-up time: 44.0 months Median OS NR (apalutamide) versus 52.2 months (placebo) (HR 0.65; 95% CI 0.53–0.79; p < 0.0001) [12] rPFS: HR 0.48 (95% CI 0.39–0.60; p < 0.001) [12] 24-month rPFS: 68.2% (apalutamide) versus 47.5% (placebo) (HR 0.484; 95% CI 0.391–0.600; p < 0.001) [41] |
| TITANe East Asia subgroup analysis (China, Japan and Korea) (n = 62) [41] | rPFS, OS |
Median follow-up time: 21.2 months (range 1.0–33.0) (apalutamide) versus 20.3 months (range 4.6–32.1) (placebo) 24-month rPFS: 76.1% (apalutamide) versus 52.3% (placebo) (HR 0.506; 95% CI 0.302–0.849; p = 0.009) |
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| nmCRPC | SPARTANf Asian subpopulation (Japan, Taiwan, and South Korea) analysis (n = 126) [44] | MFS, PSA |
Median follow-up time: Not reported MFS improvement was similar for Asian patients (HR 0.29; p < 0.001) and non-Asian patients (HR 0.28; p < 0.0001) PSA response: 82% (Asian patients) versus 91% (non-Asian patients) |
Median follow-up time: Not reported Patients with PSA not declined to < 0.2 ng/mL had a 54% risk reduction for MFS (HR 0.46; 95% CI 0.37–0.57; p < 0.0001), whereas patients with PSA that declined to < 0.2 ng/mL had an 88% risk reduction for MFS (HR 0.12, p < 0.0001) [43] Median follow-up time: 52.0 months PSA progression: HR 0.07 (95% CI 0.06–0.09; 95% CI 0.08–0.17; nominal p < 0.0001) [13] |
|
| SPARTANf Japanese subpopulation analysis (n = 55) [45] | MFS |
Median treatment duration: 5.7 months (apalutamide) versus 11.0 months (placebo) Median MFS: NR (95% CI 10.97-NE) (apalutamide) versus 18.23 months (95% CI 11.04–18.50) (placebo) |
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| Darolutamide | nmCRPC | ARAMISg Japanese subpopulation analysis (n = 95) [47] | MFS |
Median treatment duration: 14.8 months (darolutamide) versus 10.9 months (placebo) Median MFS: NR (darolutamide) versus 18.2 months (placebo) (HR 0.28; 95% CI 0.11–0.70) |
Median follow-up time: 29.0 months [6] Median MFS: 40.4 months (darolutamide) versus 18.4 months (placebo) (HR 0.41; 95% CI 0.34–0.50; 2-sided p < 0.0001) [46] |
AAP abiraterone acetate plus prednisolone, CI confidence interval, HR hazard ratio, mCNPC metastatic castration-naive PCa, mCRPC metastatic castration-resistant PCa, MFS metastasis-free survival, NHT novel hormonal therapy, nmCRPC non-metastatic castration-resistant PCa, NR not reached, OS overall survival, PSA prostate-specific antigen, rPFS radiographic progression-free survival
aLATITUDE is the study of AA plus low-dose prednisolone plus ADT versus ADT alone in newly diagnosed participants with high-risk mCNPC. bARCHES is the study of ADT with enzalutamide or placebo in men with mCNPC. cPROSPER is the study of enzalutamide in men with nmCRPC. dPREVAIL is the study of enzalutamide in men with mCRPC. eTITAN is the study of apalutamide in men with mCNPC. fSPARTAN is the study of apalutamide in men with nmCRPC. gARAMIS is the study of darolutamide in men with nmCRPC