A major Australian-led prostate cancer trial found a hormone-blocking drug dramatically reduced the risk of relapse among very high-risk men, prompting calls to change the standard of care for these patients and potentially save thousands of lives.
Adding the medication darolutamide (Nubeqa) to standard therapies for men with aggressive or treatment-resistant prostate cancer led to a 58 per cent drop in the cancer relapsing and spreading to other organs and tissue four years later, the researchers of the global phase 3 trial reported.
“We’ve seen a very strong treatment effect with decreasing relapses substantially,” said co-chair of the DASL-HiCaP trial, Professor Christopher Sweeney.
“Ultimately, we know this leads to more men living longer and dying without prostate cancer,” he said.
Darolutamide is only available and subsidised via the Pharmaceutical Benefits Scheme to treat metastatic or prostate cancer that is not responding to testosterone suppression, known as androgen deprivation therapy (ADT).
The first analysis of the trial suggests thousands more men with prostate cancer could benefit from the medication. More than 28,800 cases were diagnosed in 2025 – an estimated 38 per cent with high-risk, very-high-risk, or advanced disease every year nationally.
“Adding testosterone suppression to radiation decreases the number of men who relapse, but there are men who still break through and relapse,” said Sweeney, who is also director of the South Australian immunoGENomics Cancer Institute at the University of Adelaide.
All 1106 trial participants had very aggressive cancer, or their CT scans showed cancer had spread to lymph nodes in their pelvis, and had undergone radical prostatectomy or primary radiation therapy. The median age was 71.
All participants received ADT and radiation therapies. Half also took darolutamide, the other half a placebo.
After four years, 95 per cent of the darolutamide group had not developed metastatic prostate cancer compared to 88 per cent of the placebo group.
Fewer darolutamide participants had died of prostate cancer compared to those given a placebo (5 per cent versus 14 per cent), and deaths from other causes were no different between the two trial arms. Both trial groups reported similar side effects.
Howard Smith recalled thinking, “Well, I’m doomed,” the moment he learned that his prostate cancer had spread to nearby glands.
Smith was in his late 60s when his PSA level jumped from a significantly elevated 23 to 35 in five months. A biopsy confirmed his prostate cancer was aggressive.
“My urologist said to me: “This is not the one that you’re going to die with. This is the one that’s going to kill you.”
Smith chose radiation therapy rather than undergoing a prostatectomy first.
Considering Smith’s very high-risk level, his radiation oncologist said he was the ideal candidate for the trial.
Smith does not know whether he received darolutamide or a placebo in the double-blind trial, as investigators continue to track participants to assess their long-term survival.
“From my end, it’s turned out exceptionally well,” he said.
Smith, now 71, has been cancer-free for two years with a PSA of 0.01.
“I’m very lucky,” he said. “By the sound of it, I got in for treatment just in time.”
Darolutamide is a type of drug known as an androgen receptor pathway inhibitor. It binds to antigen receptors in prostate cancer cells, preventing testosterone or testosterone-like hormones from attaching and fuelling their growth.
“It acts like a broken key, which blocks any residual hormones from activating the receptors,” Sweeney said.
Professor Henry Woo, director of uro-oncology at Chris O’Brien Lifehouse said the results were “quite profound”.
“We’re not talking about all prostate cancer patients, but for men with very bad disease, this will change the standard of care,” Woo said.
Sweeney said the open question was what more data would Australian and international medicines regulators need to approve darolutamide for men at very high risk of relapse.
“Our job with this study is to get this drug available to patients and treating physicians … to increase the cure rate of men with high-risk prostate cancer,” he said.
Bayer Australia, the pharmaceutical company that supplies darolutamide, would need to apply for the drug’s PBS listing to be expanded to include the treatment of patients at very high risk of relapse.
Professor Ian Davis, chairman of the Australian and New Zealand Urogenital and Prostate Cancer Trials Group, the trial’s lead sponsor, said a diagnosis of very high-risk prostate cancer can be confronting for patients and their families, and the encouraging findings contributed to our understanding of how outcomes for these patients may be improved.
Common side effects of darolutamide include fatigue, skin rash, diarrhoea, high blood pressure, and elevated liver enzymes.
The trial results – not yet been peer-reviewed – will be announced on Saturday at the European Society of Medical Oncology Congress in Madrid, Spain.
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