Darolutamide prostate cancer trial cuts spread risk by 58%

A darolutamide prostate cancer trial has given men with high-risk disease a concrete reason for hope. Adding the drug to standard hormone therapy and radiation cut the chance of the cancer spreading or proving fatal by more than half, according to Orion, the drug's co-developer. The company published the full interim results on Saturday. The results, from an interim analysis of the DASL-HiCaP trial, were announced on Saturday as a late-breaking abstract at the European Society for Medical Oncology Congress.

At a median follow-up of 3.8 years, the combination produced a hazard ratio of 0.42 for metastasis-free survival measured by conventional imaging, a result the companies described as statistically strong. Four years after treatment, 95% of patients who received darolutamide were alive without distant spread, compared with 88% of those who received a placebo alongside the same hormone therapy and radiation.

What the trial tested

DASL-HiCaP is an investigator-led, randomized, placebo-controlled Phase III study run by the University of Sydney and the ANZUP Cancer Trials Group, and it is the first late-stage test of darolutamide in early prostate cancer rather than advanced disease. The darolutamide prostate cancer study enrolled 1,106 participants in Australia, New Zealand, Canada, the United States, Ireland and the United Kingdom, assigning half to darolutamide at 600 mg twice daily and half to a matching placebo, both for 96 weeks alongside hormone therapy and radiation to the prostate and pelvic lymph nodes.

In the darolutamide prostate cancer trial, secondary measures pointed the same way. The risk of prostate-specific antigen progression fell by 53% with darolutamide, and four years after treatment, 91% of patients on the drug remained free of such progression, against 83% on placebo. Survival measures also leaned toward the drug group, though the companies cautioned that follow-up continues and longer-term survival data are not yet mature.

Darolutamide works by blocking the androgen receptor, the docking point through which male hormones drive prostate tumour growth. The drug binds that receptor with high affinity and shuts down its signalling, according to Bayer, which co-develops the drug, while preclinical work and brain imaging in healthy volunteers point to a low likelihood of the drug crossing into the brain or clashing with other medicines. That profile matters for men who often take several drugs at once, and it shaped the decision to test the medicine earlier in the course of the disease.

Earlier darolutamide prostate cancer trials established the drug in advanced disease, where it is already a standard option in several settings. Three previous late-stage studies tested it in men whose cancer had already spread or resisted castration, and each showed a benefit that regulators accepted. DASL-HiCaP moves the question upstream, asking whether the same drug can keep high-risk localised disease from ever reaching that advanced stage.

Safety, and what happens next

Safety results from the darolutamide prostate cancer trial were close to what doctors already expect from the drug. Severe side effects occurred in 43% of patients who received darolutamide and 36% of those on placebo, according to Orion, while fatigue and high blood pressure were somewhat more common in the drug group and fractures slightly less common. The safety picture, the company said, matched the drug's established profile.

Darolutamide, sold as Nubeqa, is already approved in more than 85 markets for advanced prostate cancer, but the darolutamide prostate cancer use tested here is not yet approved, so the new data would need regulatory review before doctors could prescribe it in this setting. Prostate cancer is the second most common cancer in men worldwide, with more than one and a half million men diagnosed each year and hundreds of thousands dying from it, and diagnoses are projected to approach three million a year by 2040.

For patients facing high-risk disease, standard treatment already pairs radiation with hormone therapy, as covered in an earlier article on prostate surgery and radiation outcomes, yet a large share still see the cancer return or spread, which is why researchers tested adding an advanced hormone-blocking drug earlier. If the darolutamide prostate cancer results hold up in longer follow-up, regulators will weigh whether that earlier use should join the standard regimen, and the final verdict will rest on the survival data still being collected.