Medivation and Astellas Pharma announced topline results from the phase 2 TERRAIN trial comparing enzalutamide with bicalutamide in men with metastatic castration-resistant prostate cancer.  The study achieved its primary endpoint demonstrating a statistically significant increase in progression-free survival (PFS) for enzalutamide compared to bicalutamide (Hazard Ratio = 0.44; 95 per cent Confidence Interval, 0.34-0.57; p<0.0001). 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 per cent of enzalutamide-treated patients and 23.3 per cent of bicalutamide-treated patients.  Grade 3 or higher cardiac adverse events were reported in 5.5 per cent of enzalutamide-treated patients versus 2.1 per cent of bicalutamide-treated patients. 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.

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

Additional data from the phase 2 TERRAIN trial, including the secondary endpoints and further safety data, will be submitted for presentation at an upcoming medical conference

The phase 2 TERRAIN trial enrolled 375 patients in North America and Europe. The trial involved patients with metastatic prostate cancer whose disease progressed despite treatment with a luteinizing hormone-releasing hormone (LHRH) analogue therapy or following surgical castration. The primary endpoint of the trial was progression-free survival, defined as time from randomization to centrally confirmed radiographic progression, skeletal related event, initiation of new anti-neoplastic therapy or death, whichever occurs first. 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 a LHRH analogue. Targeted enrollment was completed in July 2013.

XTANDI is approved by the US Food and Drug Administration for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).

Enzalutamide is an androgen receptor inhibitor that acts on three different steps in the androgen receptor signaling pathway.