Enzalutamide extended survival in metastatic prostate cancer

CHICAGO — The second-generation androgen receptor agonist enzalutamide reduced risk for death by nearly 30% in men with chemotherapy-naive metastatic prostate cancer who progressed on androgen deprivation therapy, according to results of the phase 3 PREVAIL trial presented at the ASCO Annual Meeting.

The randomized, double blind, placebo-controlled trial included 1,717 asymptomatic or mildly symptomatic patients (median age, 72 years). The majority of patients were white and high-grade disease.

Andrew J. Armstrong

Andrew J. Armstrong, MD, MSc, FACP, associate professor of medicine and surgery at Duke Cancer Institute, and colleagues randomly assigned 872 patients to 160 mg daily enzalutamide (Xtandi, Astellas). The other 845 patients received placebo.

OS and radiological PFS served as co-primary endpoints.

Median treatment duration was 16.6 months in the enzalutamide arm and 4.6 months in the placebo arm.

Researchers performed a preplanned interim analysis after 540 deaths. At that time, the data monitoring committee recommended halting the study and allowing patients initially assigned placebo to cross over to enzalutamide treatment. At the time of unblinding, about two-thirds of patients were still receiving enzalutamide.

Forty-two percent of patients remained on the study drug at the time of data cutoff.

Results of the interim analysis showed enzalutamide treatment was associated with a statistically significant increase in OS and radiographic PFS.

At the time of the interim analysis, median follow-up for survival data was 22 months.

Results showed median OS was 32.4 months in the enzalutamide arm vs. 30.2 months in the placebo arm (HR=.71; 0.6-0.84). Risk for death at 18 months was 18% in the treatment group vs. 27% in the placebo group.

An updated survival analysis performed after 656 deaths showed 18-month OS rates of 82% in the enzalutamide arm and 73% in the placebo arm (HR=0.73; 95% CI, 0.63-0.85).

The rate of radiographic PFS at 1 year was significantly higher in the enzalutamide arm (65% vs. 14%). Median radiographic progression survival has not been reached in the enzalutamide arm but was 3.9 months in the placebo arm (HR=.19; 95% CI, 0.15-0.23).

Over time, the risk for death or progression was 35% in the treatment group vs. 86% in the placebo group.

Enzalutamide also was associated with extended median time to chemotherapy (28 months vs. 10 months), time to PSA progression (11.2 months vs. 2.8 months) and time to deterioration of quality of life (11.3 months vs. 5.6 months; P<.001).

The most frequent adverse events that occurred more frequently in the enzalutamide group were fatigue (35.6% vs. 25.8%), back pain (27% vs. 22.2%), constipation (22.2%) vs. 17.2%) and arthralgia (20.3% vs. 16%).

Incidence of hot flushes (14 vs. 12 per 100 patient-years), hypertension (11 vs. 7 per 100 patient-years) and falls (11 vs. 9 per 100 patient-years) also were higher in the enzalutamide arm.

“Enzalutamide oral, once-a-day was well tolerated over a very prolonged period of time, with nearly 20% to 30% of men still on this agent after 2 years,” Armstrong said. “Enzalutamide added to ADT after progression provides meaningful clinical benefit to men with metastatic prostate cancer.”

For more information:

Armstrong AJ. Abstract #5007. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago.

Disclosure: Armstrong reports advisory roles with Amgen, Astellas/Medivation, Bristol-Myers Squibb, Dendreon, Janssen and Sanofi; honoraria from Dendreon, Pfizer and Sanofi; and research funding from Active Biotech, Dendreon, Janssen, Medivation, Novartis, Pfizer and Sanofi.