Darolutamide Plus ADT and Radiotherapy Cuts Risk of Metastasis or Death by 58% in High-Risk Prostate Cancer
Orion Pharma has announced late-breaking data presented at the European Society for Medical Oncology (ESMO) Congress 2026.
The data showed that adding darolutamide, an androgen receptor inhibitor (ARi) originally discovered by Orion Pharma, to standard-of-care androgen deprivation therapy (ADT) and locoregional radiation therapy (RT) significantly improved metastasis-free survival based on conventional imaging (MFS-CI) compared with placebo in prostate cancer patients at high risk of recurrence. Darolutamide is not currently approved for this treatment setting. The data were presented at Presidential Symposium I at the ESMO Congress 2026 (LBA4, Saturday 24 October).
At a median follow-up of 3.8 years, the interim analysis showed a 58% reduction in the risk of metastasis or death with darolutamide plus ADT and RT compared with placebo plus ADT and RT (hazard ratio [HR] 0.42; 95% CI: 0.27–0.66; p=0.0001). The 4-year metastasis-free survival rate was 95% for patients receiving darolutamide, compared with 88% for those receiving placebo.
Secondary endpoints also showed consistent positive trends with darolutamide. There was a 53% reduction in the risk of prostate-specific antigen progression or death (PSA-PFS; HR 0.47; 95% CI: 0.33–0.67), with a 4-year PSA-PFS rate of 91% versus 83% with placebo. Hazard ratios were 0.58 for prostate cancer-specific survival (PCSS) (95% CI: 0.17–1.97; 99% vs 99% at 4 years) and 0.88 for overall survival (OS) (95% CI: 0.49–1.59; 97% vs 95% at 4 years). Follow-up for both is ongoing.
The safety profile of darolutamide was consistent with its known tolerability, and adverse events were similar to those in the placebo group. Grade ≥2 adverse events of special interest for darolutamide versus placebo were fatigue/asthenia (14% vs 10%), hypertension (7% vs 9%), fractures (2% vs 3%) and cardiac events (3% vs 3%). Any Grade ≥3 adverse event occurred in 43% of patients in the darolutamide group versus 36% in the placebo group.
Follow-up of participants is continuing and will provide further information on longer-term outcomes, including overall survival.
About the DASL-HiCaP trial (ANZUP1801)
The DASL-HiCaP trial is an investigator-initiated, randomised, placebo-controlled Phase III trial (NCT04136353). It is evaluating darolutamide added to standard-of-care ADT and locoregional radiation therapy in prostate cancer patients at high risk of recurrence. The trial is being conducted by the University of Sydney and the ANZUP Clinical Trials Group. It is the fourth Phase III trial of darolutamide, following ARAMIS, ARASENS and ARANOTE, which demonstrated darolutamide’s efficacy and safety in advanced prostate cancer. DASL-HiCaP is the first Phase III study of darolutamide in early prostate cancer.
A total of 1,106 participants across Australia, New Zealand, Canada, the United States, Ireland and the United Kingdom were randomised 1:1. They received darolutamide (600 mg twice daily) or matching placebo for 96 weeks, combined with an LHRH analogue for 96 weeks and RT to the prostate or prostate bed and pelvic lymph nodes. The primary endpoint was MFS-CI. Secondary endpoints included PSA-PFS, PCSS and OS. The protocol specified an interim analysis after 87 MFS-CI events, and follow-up is ongoing to evaluate long-term overall survival.
