The ENZAMET trial—funded in part by the drug’s manufacturer, Astellas Pharma, as well as government health agencies in Canada and Australia—enrolled more than 1,100 men (largely outside of the United States) with hormone-sensitive metastatic prostate cancer. The men were randomly assigned to ADT combined with enzalutamide or with any of three other androgen-blocking drugs.

At a median follow-up of nearly 3 years, men who received ADT plus enzalutamide had a 33% reduced risk of death, with 80% still alive compared with 72% of men treated with ADT plus another antiandrogen drug, reported the trial’s lead investigator, Christopher Sweeney, M.B.B.S., of the Dana-Farber Cancer Institute.

Men in the enzalutamide group also had better clinical progression-free survival (PFS), which the research team defined as the time until the return of disease-related symptoms, the detection of new metastases on imaging scans, or the initiation of another cancer treatment for prostate cancer, whichever came first. At 3 years, 63% of men in the enzalutamide group were alive without clinical progression of their disease, compared with 33% in the standard treatment group.

Although enzalutamide appeared to be effective regardless of whether men had high- or low-volume disease, one apparent differentiating factor was planned early treatment with docetaxel. Nearly half of the men in both treatment groups received early treatment with docetaxel and, for those men, enzalutamide was not associated with longer overall survival.

Side effects and serious side effects were more common in men treated with enzalutamide, including increased blood pressure and fatigue. In men who also received docetaxel, the rate of peripheral neuropathy was more than tripled in the enzalutamide group. Seven men treated with enzalutamide experienced seizures, compared with no men in the standard treatment group, and overall more than twice as many men receiving enzalutamide stopped treatment (33 versus 14).

From the standpoint of efficacy, similar results were seen in the TITAN trial with apalutamide. Funded by the drug’s manufacturer, Janssen Pharmaceuticals, the trial enrolled more than 1,000 men with hormone-sensitive metastatic prostate cancer, with participants randomly assigned to receive ADT along with a placebo or ADT plus apalutamide.

At 2 years of follow-up, approximately 82% of men who received ADT plus apalutamide were still alive, compared with 74% in men treated with ADT plus placebo, for a 33% reduction in the risk of death. The trial’s other primary measure was the amount time men lived without evidence on imaging scans that their disease had progressed, known as radiographic PFS. At a median follow-up of nearly 2 years, men treated with ADT plus apalutamide had a 50% improvement in radiographic PFS than men treated with ADT alone.

Rash was one of the most common side effects among men treated with apalutamide, with more than a quarter experiencing this problem. For most men, the rash did not cause symptoms, but it was still the primary reason for men stopping apalutamide treatment, Dr. Chi said.

The drug also appeared to be effective across different subgroups of patients, including men with low-volume and high-volume cancer. At the time of the last analysis of the data, Dr. Chi noted, approximately two-thirds of men in the apalutamide arm were still taking the drug.