Enzalutamide cut the rate of disease progression or death by 76% and extended progression-free survival by more than 1 year in castration-resistant prostate cancer, compared with standard bicalutamide, in a phase II trial published in the Journal of Clinical Oncology.
Currently there is no approved therapy for men with nonmetastatic castration-resistant prostate cancer. For men with metastatic disease, “bicalutamide 50 mg per day is commonly used for patients for whom androgen deprivation therapy has failed, despite the lack of randomized clinical trials showing a durable or widely experienced clinical benefit in the setting of castration resistance,” said Dr. David F. Penson of Vanderbilt University Medical Center and the Tennessee Valley Veterans Administration Medical Center, both in Nashville, and his associates.
Dr. David F. Penson
Enzalutamide is an androgen receptor inhibitor that binds to the androgen receptor as bicalutamide does, but with a tenfold greater affinity. It has improved overall survival compared with placebo in two large preliminary studies, both in the prechemotherapy and postchemotherapy settings, they noted.
The investigators compared the two agents head to head in their randomized double-blind trial at 62 sites across the United States. The study was supported by Medivation and Astellas Pharma, codevelopers of enzalutamide. A total of 198 men received enzalutamide and 198 received bicalutamide.
Enzalutamide reduced the primary endpoint, risk of disease progression or death, by 76%, compared with bicalutamide. Median progression-free survival was 19.4 months, compared with 5.7 months. The median progression-free survival was not reached among men with nonmetastatic disease taking enzalutamide, while it was 8.6 months with bicalutamide (HR, 0.24). The median progression-free survival was 16.5 months among men with metastatic disease taking enzalutamide, while it was 5.5 months with bicalutamide (HR, 0.24), Dr. Penson and his associates noted (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.64.9285).
This survival benefit occurred across all subgroups of patients. All secondary endpoints also strongly favored enzalutamide. For example, it reduced the risk of radiographic disease progression or death by 68% in metastatic disease and by 76% in nonmetastatic disease. Among men who had measurable soft-tissue metastases at baseline, 60% in the enzalutamide group showed clinically meaningful tumor shrinkage, compared with only 14% of those in the bicalutamide group.
Enzalutamide also reduced the risk of prostate-specific antigen (PSA) progression by 81%. And 81% of men taking enzalutamide achieved a PSA response of 50% or greater, compared with 31% of men taking bicalutamide.
Adverse events and serious adverse events occurred at similar rates in the two study groups. The most common adverse events for both agents were fatigue and hot flashes, but these did not affect quality of life as assessed by the FACT-P questionnaire.
“These data suggest that enzalutamide should replace bicalutamide in the treatment of men with castration-resistant prostate cancer,” Dr. Penson and his associates said.