Results from the phase III PREVAIL study show that the androgen-receptor blocker enzalutamide increases survival by 29 percent in men with metastatic castration-resistant prostate cancer (mCRPC) and delays progression of the disease by 81 percent. While preliminary results from this study were released in October 2013 after the Independent Data Monitoring Committee recommended that the study be stopped early, the data were presented in full for the first time at ASCO's 2014 Genitourinary Cancers Symposium.

"Enzalutamide is likely to become an important new treatment option that has a significant impact on the progression of prostate cancer," said lead author Tomasz Beer, MD, FACP, professor of medicine and deputy director of the Knight Cancer Institute at Oregon Health and Science University. "If approved for this indication, it will become an important standard option for use before chemotherapy in patients with asymptomatic or minimally symptomatic advanced prostate cancer."

In this double-blind, placebo-controlled phase III study, 1,717 men with mCRPC who had not previously received chemotherapy were randomized to receive enzalutamide or a placebo plus standard hormone therapy. The participants had previously received treatment for the primary tumor, such as surgery or radiation therapy, as well as hormone therapy with an LHRH agonist or a first-generation anti-androgen. The two primary endpoints are overall survival and radiographic progression-free survival. Radiographic progression free survival uses regular bone and CT scans to monitor for cancer growth.

The results showed that enzalutamide slowed or stopped cancer growth in 59 percent of patients (20 percent complete responses and 39 percent partial responses), compared with five percent of patients in the placebo arm. In addition, enzalutamide significantly delayed the need for chemotherapy. On average, patients receiving enzalutamide needed chemotherapy 17 months later than those in the placebo arm. Based on this positive interim data, the Independent Data Monitoring Committee recommended that patients on the trial receiving the placebo be offered enzalutamide.

Enzalutamide is a second generation androgen-receptor blocker, which offers more potent activity than the first generation of these agents – bicalutamide, flutamide, and nilutamide. The most common side effects included fatigue, constipation, and back and joint pain, in addition to side effects associated with hormone therapy, such as weight gain and hot flashes. Overall, enzalutamide was well tolerated – the same percentage (six percent) of patients taking enzalutamide and the placebo left the study due to side effects.