Deutenzalutamide, a novel androgen receptor inhibitor, after progression on docetaxel and abiraterone in metastatic castration-resistant prostate cancer: results from the randomized phase III HC-1119-04 trial

Why this new prostate cancer drug matters

For many men with advanced prostate cancer, powerful treatments such as hormone-blocking pills and chemotherapy can hold the disease in check for a time—but eventually the cancer learns to grow again. This study tested a next-generation drug called deutenzalutamide in men whose cancer had already pushed past two major lines of defense. The results suggest this new pill could offer extra months of control with a safety profile that may be gentler on the brain and nervous system than older medicines.

A tough stage of prostate cancer

Prostate cancer is one of the most common cancers in men worldwide, and as populations age, both new cases and deaths are expected to climb sharply in the coming decades. When the disease has spread beyond the prostate and no longer responds to standard hormone-lowering therapy, it is called metastatic castration-resistant prostate cancer. At this point, men are usually treated with modern hormone-blocking pills such as abiraterone, and often with chemotherapy like docetaxel. Yet many tumors eventually outsmart these drugs, leaving patients with few good options and a pressing need for new treatments that can slow the disease without adding heavy side effects.

A redesigned blocker of male hormones

Deutenzalutamide is closely related to enzalutamide, a widely used drug that blocks the androgen receptor—a key switch that male hormones use to drive prostate cancer growth. The new medicine is "deuterated": some of the hydrogen atoms in the original molecule are replaced with deuterium, a heavier form of hydrogen. This subtle change slows how the body breaks the drug down, allowing effective levels in the bloodstream at a lower dose and with less exposure in the brain. In early trials, deutenzalutamide showed promising tumor responses and fewer problems such as dizziness, fatigue, and other nervous system effects that can be troublesome for older patients taking enzalutamide.

How the trial was done

To see whether deutenzalutamide could help men whose cancer had already progressed on abiraterone, researchers ran a large, double-blind, placebo-controlled phase III trial at 36 hospitals across China. All 417 participants had metastatic castration-resistant disease and had previously received abiraterone; about two thirds had also been treated with docetaxel. Men were randomly assigned in a 2-to-1 ratio to receive either deutenzalutamide (80 milligrams once daily) or a matching placebo pill, while continuing basic hormone suppression. Treatment continued until scans showed the cancer was growing again or side effects became unacceptable. The main outcome was how long patients lived without clear worsening of their disease on imaging tests, known as radiographic progression-free survival.

What the researchers found

Men taking deutenzalutamide stayed free of radiographic progression longer than those taking placebo. On average, the time before clear tumor growth on scans or death was about 5.5 months with deutenzalutamide compared with 3.7 months with placebo, translating to a 42% reduction in the risk of progression or death during the study period. Importantly, a meaningful minority of men on the new drug saw much longer benefit: after one year, nearly one in three still had disease under control, compared with only about one in twenty on placebo; at two years, close to one in five in the deutenzalutamide group remained progression-free, while none in the placebo group did. When the team looked at overall survival—the length of time patients lived from the start of the study—the initial comparison did not show a clear advantage, partly because many men went on to receive additional cancer treatments after the trial drug. However, when statisticians adjusted for these later therapies using established correction methods, deutenzalutamide was linked with a meaningful survival benefit.

Side effects and safety

Nearly all patients in both groups experienced some side effects, which is expected in this very sick population, but the overall safety profile of deutenzalutamide was acceptable. Serious or severe problems were somewhat more common with the new drug than with placebo, driven mainly by anemia, cancer-related pain, and fatigue. Even so, treatment-related side effects leading to stopping the study drug occurred in fewer than one in ten patients. Particularly notable was what doctors did not see: there were no reported seizures or falls—events that are a known concern with enzalutamide and other drugs that reach higher levels in the brain. Comparisons with earlier enzalutamide trials suggest deutenzalutamide may cause fewer nervous system complaints, though those cross-trial comparisons have to be interpreted carefully.

What this means for patients

For men with advanced prostate cancer that has already resisted both modern hormone pills and chemotherapy, choices are limited and often harsh. This trial shows that deutenzalutamide can offer additional months of disease control, with a subset of patients gaining long-lasting benefit, and does so with a safety profile that appears more comfortable for the brain and nervous system. While further research is needed to compare it directly with other available treatments and to pinpoint which patients are most likely to benefit, the findings support deutenzalutamide as a promising new option in a difficult stage of prostate cancer.

Citation: Wu, J., Li, X., Gu, C. et al. Deutenzalutamide, a novel androgen receptor inhibitor, after progression on docetaxel and abiraterone in metastatic castration-resistant prostate cancer: results from the randomized phase III HC-1119-04 trial. Sig Transduct Target Ther 11, 131 (2026). https://doi.org/10.1038/s41392-026-02618-3

Keywords: metastatic prostate cancer, androgen receptor inhibitor, deutenzalutamide, hormone therapy resistance, phase III clinical trial