We evaluated the addition of darolutamide to standard of care ADT and RT for very high-risk localised or biochemically persistent/recurrent prostate cancer within 1 year after radical prostatectomy (RP).
Participants (pts) were prescribed an LHRH analog for 96 weeks plus RT to prostate/prostate bed and pelvic nodes and randomised 1:1 to darolutamide 600 mg vs placebo, twice daily for 96 weeks. The primary endpoint was metastasis-free survival based on conventional imaging with CT and/or technetium bone scan (MFS-CI, as per ICECaP surrogacy for OS). PSA-progression free survival (PFS), prostate cancer specific survival (PCSS), and overall survival (OS) were secondary endpoints. The protocol specified a single interim analysis after 87 MFS-CI events, with IDSMC review for external disclosure if the 2-sided, stratified log-rank p-value for MFS-CI was <0.012.
We randomised 1,106 pts from 30APR20 to 09AUG23 with median age 71 (IQR 65-75), pelvic nodal involvement on CT in 29%, Gleason score 9-10 in 73%, and prior RP in 15%. Median follow-up was 3.8 years (IQR 3.3 to 4.5). MFS-CI was longer amongst those assigned darolutamide vs placebo: 4-year MFS-CI 95% vs 88%, hazard ratio 0.42 (95% CI 0.27 to 0.66), 27 vs 63 events, p=0.0001. PSA-PFS, PCSS, and OS are shown below. The proportions of pts experiencing grade ≥2 of the following AE clusters of special interest (darolutamide vs placebo) were: fatigue/asthenia (14% vs 10%), hypertension (7% vs 9%), fractures (2% vs 3%), and cardiac (3% vs 3%). Any AE grade ≥3 was experienced by 43% vs 36% of pts, respectively.
Darolutamide significantly improved MFS-CI when added to ADT and loco-regional RT for very high-risk localised, or biochemically persistent/recurrent prostate cancer. Follow-up is ongoing to confirm the surrogacy of MFS-CI for OS. Table: LBA4
| DarolutamideN=553 events (event-free at 4y) | PlaceboN=553 events (event-free at 4y) | Hazard ratio (95% CI) | |
| MFS | 27 (95%) | 63 (88%) | 0.42 (0.27 to 0.66) |
| PSA-PFS | 46 (91%) | 95 (83%) | 0.47 (0.33 to 0.67) |
| PCSS | 4 (99%) | 7 (99%) | 0.58 (0.17 to 1.97) |
| OS | 21 (97%) | 24 (95%) | 0.88 (0.49 to 1.59) |
NCT04136353.
The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP).
The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Bayer, The University of Sydney, Cancer Australia.