AR antagonist increases survival vs. older agent

In men with metastatic castration-resistant prostate cancer, progression-free survival (PFS) is increased in men receiving enzalutamide (Xtandi) compared with those receiving the first-generation androgen receptor blocker bicalutamide (Casodex), study findings showed.

The phase II study, known as TERRAIN, achieved its primary endpoint, showing a statistically significant increase in PFS for enzalutamide versus bicalutamide (hazard ratio: 0.44; 95% confidence interval: 0.34-0.57; p<.0001). Median PFS was 15.7 months in the enzalutamide group compared to 5.8 months in the bicalutamide group.

The median time on treatment in TERRAIN was 11.7 months in the enzalutamide group versus 5.8 months in the bicalutamide group. Serious adverse events were reported in 31.1% of enzalutamide-treated patients and 23.3% of bicalutamide-treated patients. Grade 3 or higher cardiac adverse events were reported in 5.5% of enzalutamide-treated patients versus 2.1% of bicalutamide-treated patients.

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Two seizures were reported in the enzalutamide group and one in the bicalutamide group. The most common side effects occurring during treatment and more common in the enzalutamide-treated versus bicalutamide-treated patients included fatigue, hot flush, hypertension, diarrhea, weight decreased, and pain in extremity.

Additional data from the trial, including the secondary endpoints and further safety data, will be submitted for presentation at an upcoming medical meeting.

Next: Robust data set

“The results of this study showed that enzalutamide provides a longer duration of disease control in the studied patient population compared to bicalutamide,” TERRAIN co-principal investigator Neal Shore, MD, of Carolina Urologic Research Center, Myrtle Beach, SC, said in a news release from Medivation Inc. and Astellas Pharma Inc. “This robust data set adds to an impressive and consistent body of data for enzalutamide across multiple studies and stages of prostate cancer.”

The TERRAIN trial enrolled 375 patients in North America and Europe. It included patients with metastatic prostate cancer whose disease progressed despite treatment with luteinizing hormone-releasing hormone (LHRH) analogue therapy or following surgical castration. PFS, the primary endpoint, was defined as time from randomization to centrally confirmed radiographic progression, skeletal-related event, initiation of new anti-neoplastic therapy, or death, whichever occurs first.

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The trial was designed to evaluate enzalutamide at a dose of 160 mg taken once daily versus bicalutamide at a dose of 50 mg taken once daily, the approved dose in combination with an LHRH analogue. Targeted enrollment was completed in July 2013.

Dr. Shore is an investigator and advisory board member for Astellas and Medivation.

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