Bayer: Darolutamide with ADT and RT Cuts Metastasis-or-Death Risk 58% in High‑Risk Prostate Cancer

Trial and design

The DASL-HiCaP (ANZUP1801) investigator-initiated Phase III trial randomized 1,106 participants 1:1 to darolutamide 600 mg twice daily or matching placebo for 96 weeks, combined with an LHRH analog for 96 weeks and locoregional radiation therapy to the prostate/prostate bed and pelvic lymph nodes. The primary endpoint was metastasis-free survival by conventional imaging (MFS-CI); secondary endpoints included PSA-PFS, prostate cancer-specific survival (PCSS) and overall survival (OS). Darolutamide is not currently approved for this early treatment setting.

Primary outcome

At a median follow-up of 3.8 years, the preplanned interim analysis after 87 MFS-CI events showed darolutamide plus ADT and RT reduced the risk of metastasis or death by 58% versus placebo (HR 0.42; 95% CI: 0.27–0.66; p=0.0001). The 4-year MFS-CI rate was 95% with darolutamide versus 88% with placebo.

Secondary outcomes

Secondary analyses demonstrated a 53% reduction in risk for PSA progression (PSA‑PFS HR 0.47; 95% CI: 0.33–0.67), with 4-year PSA‑PFS rates of 91% for darolutamide versus 83% for placebo. Reported hazard ratios for PCSS and OS were 0.58 (95% CI: 0.17–1.97; 4‑year PCSS 99% vs 99%) and 0.88 (95% CI: 0.49–1.59; 4‑year OS 97% vs 95%), respectively, with follow-up ongoing.

Safety and follow-up

The safety profile was consistent with prior data; adverse-event rates were similar between arms for most events. Proportions of patients with Grade ≥2 adverse events of special interest were fatigue/asthenia 14% vs 10%, hypertension 7% vs 9%, fractures 2% vs 3%, and cardiac events 3% vs 3% (darolutamide vs placebo). Any Grade ≥3 adverse event occurred in 43% of patients receiving darolutamide versus 36% with placebo. Follow-up is continuing to assess longer-term outcomes, including overall survival.