We evaluated the effects of adding enzalutamide (ENZA) to standard adjuvant ADT with radiation therapy (RT) for high-risk, localised or locally-advanced prostate cancer (L/LAPC).
Participants (pts) having 24mo ADT and RT for high-risk L/LAPC were randomized to ENZA 160mg daily for 24 mo vs a non-steroidal anti-androgen (NSAA) for 6 mo with stratification across 7 clinico-pathological factors. Metastasis-free survival (MFS) on conventional imaging (ICECaP) was the primary endpoint. Secondary endpoints included OS, PC-specific survival (PCSS), PSA progression-free survival (PSA-PFS), clinical-PFS, and adverse events (AE). 200 MFS events provided 80% power assuming a true MFS hazard ratio (HR) of 0.67 and 2-sided alpha of 0.05. Main effects were tested with unstratified logrank p-values. Five subgroups of interest were prespecified and subgroup effects were tested with interaction p-values (i-p).
We enrolled 802 pts from MAR2014 to JUN2018: median age 71; 89% Gleason 8-10; 47% T3-4; 35% PSA≥20; and 11% N1. 207 MFS events occurred during a median follow-up of 92 mo. ENZA and NSAA had similar effects on MFS, OS, and PCSS; ENZA had larger effects on PSA-PFS and clinical-PFS (Table). Effects of ENZA on MFS were larger in 2 of the 5 pre-specified subgroups of interest: clinical N1 (i-p=0.04) and planned pelvic RT (i-p20 ng/mL), Age<70, or by region. The AEs reported for most pts (ENZA vs NSAA) were fatigue (353 vs 321), hot flashes (315 vs 281), and urinary frequency (309 vs 303). Grade 3-5 AEs occurred in 185 pts in each group.
The addition of ENZA to ADT and RT had limited effects on MFS during 8 years of follow-up in high-risk L/LAPC. Effects on MFS were larger in those with positive pelvic nodes on conventional imaging, and in those with pelvic RT planned. Clinical trials information: NCT02446444.
| Outcome at 8 years | ENZAN=401 | NSAAN=401 | HR (95% CI) | p-value (2-sided) |
| MFS | 74% | 72% | 0.88 (0.67, 1.15) | 0.34 |
| OS | 83% | 80% | 0.87 (0.63, 1.20) | 0.40 |
| PCSS | 97% | 96% | 0.90 (0.41, 1.97) | 0.79 |
| PSA-PFS | 67% | 62% | 0.78 (0.61, 0.99) | 0.04 |
| Clinical-PFS | 72% | 66% | 0.76 (0.59, 0.98) | 0.04 |
| MFS at 8 years in 2 of 5 prespecified subgroups of interest (Also stratification factors) | Interaction p-values (2-sided) | |||
| N1 subgroup | 77% (N=46) | 50% (N=42) | 0.43 (0.20-0.92) | 0.04 |
| N0 subgroup | 74% (N=355) | 75% (N-359) | 0.97 (0.72-1.30) | |
| Pelvic RT subgroup | 82% (N=162) | 65% (N=162) | 0.47 (0.29-0.76) | <0.001 |
| No pelvic RT subgroup | 69% (N=239) | 76% (N=239) | 1.25 (0.89-1.76) |
NCT02446444.