Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: Interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801)

DASL-HiCaP

Patient / Population Intervention / Exposition Vergleich Endpunkt

In patients with very high-risk localised or biochemically persistent/recurrent prostate cancer receiving ADT and radiation therapy, adding darolutamide improved metastasis-free survival on conventional imaging compared with placebo.

N

1.106Patienten

Design

International, placebo-controlled, phase 3 trial randomising 1:1 patients with very high-risk localised prostate cancer, or biochemically persistent/recurrent disease within 1 year after radical prostatectomy, all receiving 96 weeks of LHRH analogue plus RT to the prostate/prostate bed and pelvic nodes, to darolutamide vs placebo for 96 weeks (NCT04136353).

Endpunkt

Metastasis-free survival based on conventional imaging with CT and/or technetium bone scan (MFS-CI).

Ergebnis4-year MFS-CI 95% with darolutamide vs 88% with placebo, hazard ratio 0.42 (95% CI 0.27-0.66), 27 vs 63 events, P = 0.0001. 4-year PSA-PFS 91% vs 83%, hazard ratio 0.47 (95% CI 0.33-0.67), 46 vs 95 events. 4-year PCSS 99% vs 99%, hazard ratio 0.58 (95% CI 0.17-1.97), 4 vs 7 events. 4-year OS 97% vs 95%, hazard ratio 0.88 (95% CI 0.49-1.59), 21 vs 24 events. Any grade ≥3 AE 43% vs 36%. Grade ≥2 fatigue/asthenia 14% vs 10%, hypertension 7% vs 9%, fractures 2% vs 3%, cardiac 3% vs 3%.

Niazi T, Thomas H, Zhang A, et al. Presented at ESMO Congress 2026, abstract LBA4, 24 October. Not yet published.

Diskussion & Kritik

This placebo-controlled phase 3 trial shows that adding darolutamide to ADT and locoregional RT clearly lengthened metastasis-free survival on conventional imaging. The result comes from the single interim analysis at a median follow-up of 3.8 years, and the primary endpoint is a surrogate: overall survival and prostate cancer specific survival show no clear difference so far (OS hazard ratio 0.88, 95% CI 0.49-1.59), with few events. Grade ≥3 adverse events were more frequent with darolutamide (43% vs 36%), and the abstract gives no detail beyond selected AE clusters. Only 15% had prior prostatectomy, so the abstract cannot say whether the benefit holds in the salvage setting, and it reports no subgroup results.