Bayer reports Phase 3 DASL-HiCaP results showing darolutamide reduced metastasis or death risk by 58% in high-risk prostate cancer. Overall survival remains uncertain.
Written By: Anamika Koshti, PharmD
Reviewed By: Pharmacally Editorial Team
Bayer has reported positive interim results from the Phase 3 DASL-HiCaP trial (NCT04136353), showing that adding the androgen receptor inhibitor darolutamide to androgen deprivation therapy (ADT) and radiotherapy significantly improved metastasis-free survival (MFS) in men with high-risk prostate cancer. At a median follow-up of 3.8 years, the combination reduced the risk of metastasis or death by 58% compared with placebo plus ADT and radiotherapy. The findings were presented as a late-breaking abstract (LBA4) at the ESMO Congress 2026. Darolutamide is not currently approved for this treatment setting.
From Advanced Disease to Earlier Intervention
DASL-HiCaP is the first Phase 3 trial evaluating darolutamide in this earlier prostate cancer setting and extends its clinical development beyond advanced disease. Previous Phase 3 studies include ARAMIS (NCT02200614) in non-metastatic castration-resistant prostate cancer, ARASENS (NCT02799602) in metastatic hormone-sensitive disease with docetaxel, and ARANOTE (NCT04736199) in metastatic hormone-sensitive disease without docetaxel.
The investigator-initiated DASL-HiCaP study was conducted in collaboration with the University of Sydney and the ANZUP Clinical Trials Group. Bayer and Orion jointly develop darolutamide.
Trial Design and Treatment
The trial enrolled 1,106 participants across Australia, New Zealand, Canada, the United States, Ireland and the United Kingdom. Participants were randomized 1:1 to receive darolutamide 600 mg twice daily or matching placebo for 96 weeks. Both groups received ADT with a luteinizing hormone-releasing hormone (LHRH) analogue for 96 weeks and radiotherapy according to the study protocol.
The primary endpoint was metastasis-free survival assessed using conventional imaging (MFS-CI). The protocol specified an interim analysis after 87 MFS-CI events.
Metastasis-Free Survival Improves at Interim Analysis
At a median follow-up of 3.8 years, darolutamide reduced the risk of metastasis or death by 58% compared with placebo (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.27–0.66; p=0.0001).
Four-year MFS was 95% with darolutamide and 88% with placebo, an absolute difference of seven percentage points. The reported event counts were 27 in the darolutamide group and 63 in the placebo group.
These findings establish a statistically significant improvement in the trial’s primary endpoint at the interim analysis. However, the results reflect MFS assessed by conventional imaging and should not be interpreted as evidence of an established overall-survival benefit.
PSA Progression Improves, but Survival Data Remain Immature
Darolutamide also improved PSA progression-free survival, reducing the risk of progression by 53% (HR, 0.47; 95% CI, 0.33–0.67). Four-year PSA progression-free survival was 91% with darolutamide versus 83% with placebo.
Overall-survival and prostate cancer-specific survival estimates remain imprecise. The HR for prostate cancer-specific survival was 0.58 (95% CI, 0.17–1.97), with four-year estimates of 99% in both groups. For overall survival, the HR was 0.88 (95% CI, 0.49–1.59), with four-year survival of 97% versus 95%.
The confidence intervals for both survival outcomes include no treatment effect. Longer follow-up is therefore needed to determine whether the improvement in MFS translates into a survival advantage.
Safety Profile and Adverse Events
Bayer described the safety profile as consistent with darolutamide’s known tolerability. Grade 2 or higher events of special interest included fatigue or asthenia (14% versus 10%), hypertension (7% versus 9%), fractures (2% versus 3%) and cardiac events (3% in both groups), for darolutamide and placebo, respectively.
However, Grade 3 or higher adverse events occurred in 43% of patients receiving darolutamide compared with 36% receiving placebo. This difference warrants consideration when assessing the potential benefits of adding treatment for 96 weeks.
Wider Development Program
Darolutamide is also being investigated in the Phase 3 ARASTEP trial (NCT05794906), which evaluates darolutamide plus ADT against ADT alone in hormone-sensitive prostate cancer with high-risk biochemical recurrence. Bayer’s announcement did not specify a regulatory filing timeline for the DASL-HiCaP results.
Clinical Interpretation
DASL-HiCaP provides evidence that adding darolutamide to ADT and radiotherapy improves MFS in men with high-risk prostate cancer. The HR of 0.42, seven-percentage-point difference in four-year MFS and improvement in PSA progression-free survival support further evaluation of this treatment approach.
The findings nevertheless require cautious interpretation. The analysis was conducted at an interim event threshold, overall and prostate cancer-specific survival data remain immature, and Grade 3 or higher adverse events were more frequent with darolutamide. Longer follow-up will clarify the durability of the MFS benefit and whether it translates into improved survival. The results support darolutamide as a potential treatment intensification option, but do not establish a survival benefit or a new approved indication.
References
Darolutamide plus ADT and radiation therapy reduces risk of metastasis or death by 58% in prostate cancer patients at high risk of recurrence. Bayer. October 24, 2026
Darolutamide Augments Standard Therapy for Localised Very High-Risk Cancer of the Prostate (DASL-HiCaP), ClinicalTrials.gov ID NCT04136353
About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.