Table 2.
Bone-related efficacy endpoints
| Drug | Trial | Endpoint | NHT vs placebo |
| M0 CRPC at high risk for metastases | |||
| Enzalutamide | PROSPER48 | MFS PROs |
36.3 vs 14.7 months (HR for metastasis or death 0.29, 95% CI 0.24 to 0.35, p<0.001) Similar clinically meaningful deterioration of HRQoL |
| Apalutamide | SPARTAN49 56 | MFS PFS2 Median time to symptomatic progression PROs |
40.5 vs 16.2 months (HR for metastasis or death 0.28, 95% CI 0.23 to 0.35, p<0.001) 55.6 vs 43.8 months (HR 0.55, 95% CI 0.45 to 0.68, p<0.0001) NR vs NR (HR 0.45, 95% CI 0.32 to 0.63, p<0.001) Stable overall HRQoL over time, similar between groups |
| Darolutamide | ARAMIS46 | Median MFS | 40.4 vs 18.4 months (HR for metastasis or death 0.41, 95% CI 0.34 to 0.50, p<0.001) |
| Median time to pain progression | 40.3 vs 25.4 months (HR 0.65, 95% CI 0.53 to 0.79, p<0.001) | ||
| Median time to first symptomatic SRE | NR in either group (16 vs 18 events, HR 0.43, 95% CI 0.22 to 0.84, p=0.01) | ||
| M1 HSPC | |||
| AAP | LATITUDE57 58 61 62 100 | Median rPFS Median time until pain progression Median time to next symptomatic skeletal events PROs |
33.0 vs 14.8 months (HR 0.47, 95% CI 0.39 to 0.55, p<0.001) 47.4 vs 16.6 months (HR 0.72, 95% CI 0.61 to 0.86, p=0.0002) NR vs NR (HR 0.75, 95% CI 0.60 to 0.95, p=0.0181) Clinical benefit in pain progression, PCa symptoms, fatigue, functional decline and overall HRQoL |
| Apalutamide | TITAN101 | Median rPFS 2-year OS rate |
NR vs 22.1 months (HR 0.48, 95% CI 0.39 to 0.60, p<0.0001) 82% vs 73% |
| M1 CRPC | |||
| AAP | COU-AA-30199 102 | Median rPFS Median time to the first SRE Pain |
5.6 vs 3.6 months (HR 0.67, 95% CI 0.58 to 0.78, p<0.001) 25.0 vs 20.3 months (HR 0.62, 95% CI 0.48 to 0.80, p=0.0001) Significant improvement in pain relief and delay of pain progression |
| AAP | COU-AA-30267 103 104 | Median rPFS Median time to opiate use for cancer-related pain PROs |
16.5 vs 8.2 months (HR 0.52, 95% CI 0.45 to 0.61, p<0.0001) NR vs 23.7 months (HR 0.71, 95% CI 0.59 to 0.85, p=0.0002) Consistent pattern of delays in pain progression and significant delayed degradation in FACT-P total scores (p=0.005) |
| Enzalutamide | AFFIRM59 | rPFS Time to the first SRE QoL response rate |
8.3 vs 2.9 months (HR 0.40, 95% CI 0.35 to 0.47, p<0.001) 16.7 vs 13.3 months (HR 0.69, 95% CI 0.57 to 0.84, p<0.001) 43% vs 18%, p<0.001 |
| Enzalutamide | PREVAIL60 | Median rPFS First SRE occurrence Median time to QoL deterioration |
NR vs 3.9 months (HR 0.19, 95% CI 0.15 to 0.23, p<0.001) 32% vs 37% at 31 months, (HR 0.72, p<0.001) 11.3 vs 5.6 months (HR 0.63, 95% CI 0.54 to 0.73, p<0.001) |
AAP, abiraterone acetate plus prednisone; CRPC, castration-resistant prostate cancer; FACT-P, Functional Assessment of Cancer Therapy–Prostate; HRQoL, health-related quality of life; HSPC, hormone-sensitive prostate cancer; M0, non-metastatic; M1, metastatic; MFS, metastasis-free survival; NHT, novel hormone therapy; NR, not reached; OS, overall survival; PCa, prostate cancer; PFS2, progression-free survival on next-line therapy; PRO, patient-reported outcome; QoL, quality of life; rPFS, radiographic progression-free survival; SRE, skeletal-related event.