In the phase III PREVAIL study, taking enzalutamide prior to chemotherapy improved survival and slowed progression of metastatic castration-resistant prostate cancer. The FDA is now considering an application to expand the drug's use to the pre-chemotherapy setting.
When given before chemotherapy, the prostate cancer drug enzalutamide (Xtandi) improved survival and delayed tumor progression in men with metastatic disease that had progressed on androgen deprivation therapy. Researchers reported the finding at the European Association of Urology (EAU) 29th Annual Congress in Stockholm, Sweden, in April.
Based on the findings, drugmakers Astellas Pharma and Medivation have requested permission from the FDA to use enzalutamide before chemotherapy. The FDA approved enzalutamide, a second-generation androgen-receptor inhibitor, in 2012 for use after docetaxel chemotherapy.
The phase III PREVAIL study included 1,717 men from various countries with metastatic castration-resistant prostate cancer (CRPC) that was causing mild or no symptoms. Across the entire cohort, a daily oral dose of enzalutamide reduced the risk of death by 29% and cut the risk of radiographically detected disease progression by 81% compared with placebo.
Enzalutamide also delayed the median time before men needed chemotherapy by 17 months compared with placebo (28 months versus 10.8 months). That means the tens of thousands of men with metastatic CRPC who have few, if any, symptoms could take a pill and postpone toxic chemotherapy, says the study's co-principal investigator Tomasz Beer, MD, professor of medicine and deputy director of the Knight Cancer Institute at Oregon Health & Science University in Portland.
Enzalutamide was well tolerated in the study, with more fatigue, back pain, constipation, and arthralgia reported in patients treated with enzalutamide than placebo.
Looking at the subpopulation of European men, data presented at the EAU meeting showed efficacy and safety outcomes that were consistent with those of the entire cohort.
Beer says the typical U.S. patient with metastatic CRPC starts with abiraterone (Zytiga; Janssen Biotech), an antiandrogen approved for use both before and after chemotherapy. Pending FDA approval, enzalutamide would become another option in the first-line setting.
Enzalutamide and abiraterone have not been compared head to head, but certain patient factors could help guide treatment decisions, Beer says. For example, abiraterone must be given with prednisone, a steroid that can raise blood pressure and blood glucose levels. “If you have diabetes or hypertension, then enzalutamide might be a better option,” he says. For patients with a history of seizures, abiraterone might be the better choice since the PREVAIL study excluded patients at risk for seizures.
Researchers are now testing enzalutamide in other settings, including after radical prostatectomy and in combination with abiraterone for men with metastatic CRPC.
Regardless of which drug ultimately takes the lead in the pre-chemotherapy setting, both are effective, convenient, and safe for men with metastatic CRPC, Beer says. “These drugs can control the disease for a year or two, whereas in the past with chemotherapy if we could control the disease for 4 to 6 months, that was success. It's a whole different disease than it was 5 years ago.”