(ChemotherapyAdvisor) – The oral androgen-receptor–signaling inhibitor enzalutamide (MDV3100) “significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy by a median of 4.8 months and reduced the risk of death from any cause by 37% versus placebo,” a study concluded in New England Journal of Medicine online August 15.
From September 2009 through November 2010, the phase 3 study randomly assigned 1,199 men in a 2:1 ratio to enzalutamide 160mg/day (n=800) or placebo (n=399). Study participants were stratified by ECOG performance status and pain intensity, noted Howard I. Scher, MD, and colleagues for the AFFIRM (A Study Evaluating the Efficacy and Safety of the Investigational Drug MDV3100) Investigators.
After a planned interim analysis at 520 deaths, the study was stopped, they reported. In the enzalutamide group, median overall survival, the primary end point, was 18.4 months (95% CI, 17.3–not yet reached) vs 13.6 months (95% CI, 11.3–15.8) in the placebo group (HR for death in the enzalutamide group, 0.63; 95% CI, 0.53–0.75; P<0.001).
“In a multivariate analysis, the survival benefit was seen in all patient subgroups, including those stratified according to age and ECOG performance status, the geographic location of the study center, the extent of disease on diagnostic imaging, and biochemical measurements that included PSA and lactate dehydrogenase, even after adjustment for baseline factors,” Dr. Scher wrote.
Compared with placebo, enzalutamide significantly improved the proportion of patients with a reduction in PSA level by 50% or more (54% vs 2%), the soft-tissue response rate (29% vs 4%), the quality-of-life response rate (43% vs 18%), time to PSA progression (8.3 vs 3.0 months; HR 0.25), radiographic progression-free survival (8.3 vs 2.9 months; HR 0.40), and time to first skeletal-related event (6.7 vs 13.3 months; HR 0.69); all P<0.001.
Patients in the enzalutamide group reported higher rates of fatigue, diarrhea, and hot flashes; 5 (0.6%) had seizures.
“These data confirm the central role of the androgen receptor and androgen-receptor signaling in the progression of prostate cancer throughout the spectrum of disease,” the authors reported. “This novel agent is anticipated to join the therapeutic armamentarium of anticancer drugs with diverse mechanisms of action that confer a survival benefit in men with castration-resistant prostate cancer.”
Enzalutamide is also being studied in earlier-stage prostate cancer.