Bayer Darolutamide Cuts Metastasis or Death Risk 58% in Phase III Trial

Bayer announced on October 24, 2026, that interim results from the Phase III DASL-HiCaP trial showed its androgen receptor inhibitor darolutamide, added to standard-of-care androgen deprivation therapy (ADT) and locoregional radiation therapy, reduced the risk of metastasis or death by 58% compared with placebo plus ADT and radiation therapy in prostate cancer patients at high risk of recurrence. The data are scheduled for presentation as late-breaking abstract LBA4 in Presidential Symposium I at the European Society for Medical Oncology (ESMO) Congress 2026 on Saturday, October 24, 2026, at 16:30 CET.

At a median follow-up of 3.8 years, the interim analysis showed a hazard ratio of 0.42 for the combined primary endpoint of metastasis-free survival based on conventional imaging (MFS-CI), with a 95% confidence interval of 0.27 to 0.66 and p=0.0001, according to Bayer’s announcement. The four-year metastasis-free survival rate was 95% for patients receiving darolutamide compared with 88% for those receiving placebo. Bayer stated that darolutamide is currently not approved for this treatment setting.

Secondary endpoints also showed consistent positive trends with darolutamide, the company reported. Prostate-specific antigen progression-free survival (PSA-PFS) showed a 53% reduction in risk, with a hazard ratio of 0.47 and a 95% confidence interval of 0.33 to 0.67; the four-year PSA-PFS rate was 91% versus 83% with placebo. Prostate cancer-specific survival and overall survival hazard ratios were 0.58 (95% CI: 0.17 to 1.97; 99% versus 99% at four years) and 0.88 (95% CI: 0.49 to 1.59; 97% versus 95% at four years), respectively, with follow-up ongoing.

“The clear improvement in metastasis-free survival seen in interim results from the DASL-HiCaP trial highlights the potential of adding darolutamide to standard androgen deprivation therapy and radiation therapy to help prevent or delay disease progression in patients who are at high risk of progression despite receiving primary curative therapy,” said Dr. Tamim Niazi, Associate Professor of Oncology at McGill University, Radiation Oncologist at the Jewish General Hospital in Montreal, Canada, and Co-Lead Investigator of the study.

Bayer reported that the safety profile of darolutamide was consistent with its known tolerability, with adverse events similar to the placebo group. Proportions of patients experiencing Grade 2 or higher adverse events of special interest for darolutamide versus placebo were fatigue/asthenia at 14% versus 10%, hypertension at 7% versus 9%, fractures at 2% versus 3%, and cardiac events at 3% versus 3%. Any Grade 3 or higher adverse event occurred in 43% of patients in the darolutamide group versus 36% in the placebo group.

Trial Design and Governance

DASL-HiCaP (ANZUP1801; NCT04136353) is an investigator-initiated, randomized, placebo-controlled Phase III trial evaluating darolutamide added to standard-of-care ADT and locoregional radiation therapy in prostate cancer patients at high risk of recurrence. A total of 1,106 participants across Australia, New Zealand, Canada, the United States, Ireland, and the United Kingdom were randomized 1:1 to receive darolutamide at 600 mg twice daily or matching placebo for 96 weeks, combined with an LHRH analog for 96 weeks and radiation therapy to the prostate or prostate bed and pelvic lymph nodes. The primary endpoint was MFS-CI, and the protocol specified the interim analysis after 87 MFS-CI events.

According to ANZUP’s DASL-HiCaP trial page, the University of Sydney is the trial sponsor and the NHMRC Clinical Trials Centre is the global coordinating centre, with Professor Christopher Sweeney and Associate Professor Tamim Niazi serving as study chairs. The enrolled population comprised adults aged 18 years or older with very high-risk localised prostate cancer, or very high-risk features with PSA persistence or rise within one year following radical prostatectomy, who were suitable for radiotherapy. Recruitment is closed and the trial is in follow-up. Collaborating groups included the Canadian Cancer Trials Group, Cancer Trials Ireland, Memorial Sloan Kettering Cancer Center, and the Prostate Cancer Clinical Trials Consortium, and ANZUP acknowledges Bayer for providing funding and study drug for the trial.

“By advancing darolutamide into earlier disease settings, we aim to reach more patients across the prostate cancer care continuum,” said Christine Roth, Executive Vice President, Global Product Strategy and Commercialization at Bayer’s Pharmaceuticals Division. Roth said the company is proud to support ANZUP, the Sydney Clinical Trials Centre, CCTG, and international partners in the research.

Development Program and Regulatory Footprint

DASL-HiCaP is the fourth Phase III trial of darolutamide and the first in early prostate cancer, following ARAMIS, ARASENS, and ARANOTE, which demonstrated the drug’s efficacy and safety in advanced prostate cancer, according to Bayer. Under the brand name Nubeqa plus ADT, darolutamide is approved in more than 85 markets worldwide, including the US, EU, and China. It is approved for adult patients with mHSPC with docetaxel in more than 85 countries, for mHSPC without docetaxel in 75 markets, and for adult patients with nmCRPC at high risk of developing metastatic disease in more than 85 countries. Darolutamide is developed jointly by Bayer and Orion Corporation, a Finnish pharmaceutical company.

The ongoing Phase III ARASTEP trial is evaluating darolutamide plus ADT compared with ADT alone in hormone-sensitive prostate cancer patients with high-risk biochemical recurrence who have no evidence of metastatic disease by conventional imaging and a positive PSMA PET/CT at baseline. Bayer describes darolutamide as an oral androgen receptor inhibitor with a distinct chemical structure that binds with high affinity to the androgen receptor, and states that preclinical models and neuroimaging data in healthy humans support its low potential for blood-brain barrier penetration and low potential for clinically relevant drug-drug interactions. The company’s marketed prostate cancer franchise also includes Xofigo alongside Nubeqa.

Prostate cancer is the second most common cancer and the fourth most common cause of cancer death in men worldwide, with over 1.5 million men diagnosed each year and almost 420,000 dying from the disease worldwide, according to the announcement, which states that diagnoses are projected to increase to 2.9 million by 2040. Standard therapy for patients at high risk of recurrence combines radiation therapy with ADT, though a significant proportion of patients experience treatment failure, local recurrence, or distant metastases despite this approach.