Enzalutamide Outperforms Bicalutamide in the Treatment of Men with Prostate Cancer

Enzalutamide (Xtandi) outperformed bicalutamide (Casodex) in 2 separate phase 2 clinical trials of men with prostate cancer, according to data presented at the 2015 American Urological Association annual meeting.

Enzalutamide was associated with longer progression-free survival (PFS) and a greater benefit in health-related quality of life compared with bicalutamide in men with metastatic castration-resistant prostate cancer (CRPC) in the TERRAIN trial, said Arnauld A. Villers, MD, PhD, Professor of Urology, University of Lille, France.

All 375 patients had asymptomatic or mildly symptomatic metastatic CRPC that had progressed after treatment with a luteinizing hormone-releasing hormone analog or after surgical castration. The patients were randomized to enzalutamide 160 mg daily or to bicalutamide 50 mg daily.

To be eligible, patients had to have ≥2 bone lesions or soft-tissue disease, progressive disease, ongoing gonadotropin-releasing hormone analog therapy or surgical castration, and a life expectancy of ≥1 years.

The median PFS, the primary end point, was 15.7 months in the enzalutamide arm compared with 5.8 months in the bicalutamide arm, corresponding to a hazard ratio of 0.44 (P <.001). “The separation between the 2 curves was seen early, at 3 months,” said Dr Villers.

At week 13, 82% of patients receiving enzalutamide had a prostate-specific antigen (PSA) response (≥50% reduction) versus 21% of patients in the bicalutamide arm, and 56% of patients had a PSA reduction of ≥90% versus 5% of patients in the bicalutamide arm. “Half of the patients in the enzalutamide arm reached a ≥90% decrease in PSA by month 6,” Dr Villers said.

Enzalutamide was also significantly superior to bicalutamide in 5 of 7 quality-of-life domains. The quality of life was maintained for a significantly longer time in the enzalutamide group, said Dr Villers.

Exposure to enzalutamide was double that seen with bicalutamide, a median of 11.7 months versus 5.8 months, respectively. The rates of serious adverse events were 31% in the enzalutamide arm and 23% in the bicalutamide arm. There were 3 seizures overall—2 in the enzalutamide arm and 1 in the bicalu­tamide arm.

In a second randomized, phase 2 study, known as STRIVE, enzalutamide was superior to bicalutamide as an add-on to androgen-deprivation therapy in men with nonmetastatic CRPC or metastatic CRPC, said Celestia S. Higano, MD, Professor of Medicine and Urology, University of Washington, Seattle.

In STRIVE, 396 patients were randomized to enzalutamide or bica­lutamide at the same dosages that were used in TERRAIN.

The median PFS was 19.4 months in men receiving enzalutamide versus 5.7 months in those receiving bicalutamide (P <.001). The time to PSA progression also favored enzalutamide.

In the enzalutamide arm, 81% of the patients had a ≥50% decline in PSA level compared with only 31% in the bicalutamide arm, and 65% in the enzalutamide arm had a ≥90% decrease in PSA levels compared with 9% in the bicalutamide arm.

“The enzalutamide arm is superior to the bicalutamide arm…on both the primary and key secondary end points,” said Dr Higano.

The median durations of treatment were 14.7 months in the enzalutamide arm versus 8.4 months in the bicalutamide arm.