CATEGORY: MEN’S HEALTH
A man whose prostate cancer has spread usually starts on hormone therapy that strips away most of his testosterone, and for a while the cancer stalls. Adding a second drug, the pill darolutamide, cut the risk of cancer progression or death by 46% in men at that stage.1 Two years in, 70.3% of men on darolutamide showed no progression on imaging, against 52.1% on placebo. That is roughly 18 more men in every 100 still holding the disease in check.
A Second Lock on the Fuel Line
Prostate cancer runs on male hormones, chiefly testosterone, the way an engine runs on fuel. The standard treatment for cancer that has spread is androgen-deprivation therapy, medicine that sharply lowers the body’s own testosterone production. It shuts off most of the supply. Cancer cells can still wring use out of the trickle that remains. Darolutamide, a twice-daily pill, blocks the receptor the hormone plugs into. Even that trickle can no longer reach the engine.
Two Pills Handed Out for Every One Placebo
The trial, called ARANOTE, enrolled 669 men with metastatic hormone-sensitive prostate cancer, meaning cancer that has spread beyond the prostate but still answers to hormone therapy. Allocation ran two to one, darolutamide or an identical-looking placebo added to hormone therapy, and nobody on either side of the exam room knew which. Regular imaging scans then recorded whose cancer advanced and when, the study’s main measure. Among men on placebo, the typical time to progression on scans was about 25 months. In the darolutamide group it had not been reached when the results were analyzed.
PSA Dropped Further, Resistance Came Later
The pill’s advantage carried through the trial’s other measures. PSA is a blood protein made by prostate tissue that doctors use to follow the cancer’s activity. It fell to very low levels in 62.6% of men on darolutamide against 18.5% on placebo. The drug also cut by 60% the risk of the cancer turning castration-resistant, the stage at which it grows despite hormone therapy. Side effects came out even. Serious adverse events hit about 31% of both groups, and fewer men stopped darolutamide for side effects (6.1%) than stopped placebo (9.0%).
Survival Numbers Still Filling In
Deaths were 19% less frequent in the darolutamide group so far, but that difference was not statistically conclusive. The survival data are still maturing, and longer follow-up will settle it. The rest of the evidence points the same way. ARASENS found that darolutamide combined with hormone therapy and chemotherapy extended survival in this disease,2 and trials of similar hormone-receptor blockers have landed in the same place. What ARANOTE adds is the benefit without chemotherapy in the mix. US regulators have since approved darolutamide for this use.
Key Takeaways
- Adding darolutamide to hormone therapy cut the risk of imaging-confirmed progression or death by 46% among 669 men with metastatic hormone-sensitive prostate cancer. At two years, 70.3% versus 52.1% remained progression-free.
- Side effects were similar to placebo, and fewer men on darolutamide stopped treatment because of them.
- Survival results are not yet mature. The finding matches earlier darolutamide research, including the ARASENS trial, and darolutamide now carries US approval for this setting.
References
- Saad F, Vjaters E, Shore N, et al. Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial. Journal of Clinical Oncology. 2024;42:4271–4281. link
- Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. The New England Journal of Medicine. 2022;386(12):1132–1142. link