The men were randomized evenly to double-blind treatment with enzalutamide (160 mg/day) or a placebo.
With a median follow-up of about 20 months, enzalutamide was associated with better overall survival (hazard ratio, 0.71; P less than .0001) and better radiographic progression-free survival (HR, 0.19; P less than .0001). In post hoc analyses, the findings were much the same in the small subset of patients who had visceral metastases, according to Dr. Beer.
The response rate was 59% with enzalutamide (20% complete response; 39% partial response), compared with just 5% with placebo (P less than .0001).
Enzalutamide also delayed the median time to receipt of chemotherapy – "a pragmatic measure of real-world treatment effect," he noted – from 11 to 28 months (HR, 0.35; P less than .0001).
The rate of grade 3 or worse adverse events was 43% with enzalutamide and 37% with placebo. The most common toxicities of any grade were fatigue, back pain, constipation, and arthralgia. The rate of treatment discontinuation from adverse events was identical at 6% in each arm.
Two patients (0.1%) – one in each study arm – experienced seizure, which has been a concern with enzalutamide; both were subsequently determined to have a history of seizure unknown to their enrolling physician, which would have excluded them from the trial.
"What that tells us is that with appropriate patient selection, this clinical trial demonstrates that the drug can be administered very safely from the perspective of seizure risk," Dr. Beer said. "In point of fact, in patients who didn’t have a prior history of seizures, there were no seizures at all in this trial."
Dr. Beer disclosed that he receives research funding from Cougar Biotechnology, Janssen Biotech, Astellas Pharma, and Medivation. The trial was sponsored by Medivation.