Enzalutamide resulted in a 71% reduction in metastatic disease risk among men with castration-resistant prostate cancer (CRPC) and rapid prostate-specific antigen (PSA) doubling time, according to the first interim analysis of data from the phase III PROSPER trial. The findings were presented (abstract 3) at the 2018 Genitourinary Cancers Symposium, held February 8–10 in San Francisco.
The median PSA doubling time for men in the study was 3.7 months, reported lead study author Maha Hussain, MD, FACP, FASCO, of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University’s Feinberg School of Medicine in Chicago.
“Therapy was well tolerated; adverse events were generally consistent with those reported in prior clinical trials in men with CRPC,” Dr. Hussain said.
Treatment for nonmetastatic CRPC represents an “unmet need,” with no therapies currently approved by the US Food and Drug Administration, Dr. Hussain said. Rapid PSA doubling time (≤ 10 months) is predictive of the development of metastatic disease in these patients. Delaying the onset of metastasis can prolong overall survival.
The PROSPER study authors sought to determine whether enzalutamide would prolong metastasis-free survival (MFS) among men with CRPC with PSA doubling times of 10 or fewer months. A total of 1,401 men were randomized 2:1 to receive androgen deprivation therapy plus either enzalutamide (160 mg/day) or placebo. The study arms were well balanced for baseline patient characteristics, with both groups representing older patients (aged 50-95 years in the enzalutamide group and 53–92 years in the placebo group).
Median MFS was 36.6 months with enzalutamide vs 14.7 months with placebo (hazard ratio [HR], 0.29; 95% CI, 0.24–0.35; P < .0001). Patients in the enzalutamide group also saw significantly prolonged time to PSA progression (median 37.2 vs 3.9 months; HR, 0.07; 95% CI, 0.05–0.08; P < .0001) and time to first use of new antineoplastic therapy (median 39.6 vs 17.7 months; HR, 0.21; 95% CI, 0.17–0.26; P < .0001), two secondary study endpoints.
“The proportion of progression events in the enzalutamide arm was 50% less than that of the placebo arm,” Dr. Hussain said. “Median MFS was 22 months longer with enzalutamide than with placebo.”
Median overall survival was not reached for either group but patients in the enzalutamide group had a 20% lower relative mortality risk than those in the placebo group.