Astellas Pharma Inc. and Medivation, Inc. announced topline results from the phase 2 STRIVE trial comparing enzalutamide with bicalutamide in a study population of men with non-metastatic or metastatic castration-resistant prostate cancer. The study achieved its primary endpoint demonstrating a statistically significant increase in progression-free survival (PFS) for enzalutamide compared with bicalutamide (Hazard Ratio = 0.24; 95% Confidence Interval, 0.18-0.32; p<0.0001). Median PFS was 19.4 months in the enzalutamide group compared with 5.7 months in the bicalutamide group.

Astellas is a pharmaceutical company dedicated to improving the health of people around the world.

The median time on treatment in the STRIVE trial was 14.7 months in the enzalutamide group versus 8.4 months in the bicalutamide group. Serious adverse events were reported in 29.4% of enzalutamide-treated patients and 28.3% of bicalutamide-treated patients. Grade 3 or higher cardiac adverse events were reported in 5.1% of enzalutamide-treated patients versus 4.0% of bicalutamide-treated patients. One seizure was reported in the trial in the enzalutamide-treated group and none in the bicalutamide-treated group. The most common side effects noted more frequently in the enzalutamide-treated versus bicalutamide-treated patients included fatigue, back pain, hot flush, fall, hypertension, dizziness, and decreased appetite, consistent with the known safety profile of enzalutamide.

"These results demonstrate the potential for enzalutamide to provide a longer duration of disease control compared with bicalutamide in the studied patient population," said David Penson, M.D., MPH, co-principal investigator of the STRIVE study, Director of the Center for Surgical Quality and Outcomes Research and Chair of the Department of Urologic Surgery of Vanderbilt University Medical Center.  

The STRIVE study is the second of two head-to-head studies of enzalutamide versus bicalutamide, the first of which was TERRAIN. Additional results from the STRIVE trial, including the secondary endpoints and safety data, will be submitted for presentation at upcoming medical conferences.

The phase 2 STRIVE trial enrolled 396 castration-resistant prostate cancer patients in the United States. The trial randomized 257 patients with metastatic prostate cancer and 139 patients with non-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 radiographic (bone or soft tissue) progression, PSA progression (defined by Prostate Cancer Working Group 2 criteria), or death due to any cause, 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.

The phase 2 TERRAIN trial enrolled 375 patients in North America and Europe. The trial randomized 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.

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.

In October 2009, Medivation and Astellas entered into a global agreement to jointly develop and commercialize enzalutamide. The companies are collaborating on a comprehensive development program that includes studies to develop enzalutamide across the full spectrum of advanced prostate cancer as well as advanced breast cancer. The companies jointly commercialize Xtandi in the United States and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing Xtandi outside the United States.

Astellas Pharma Inc. is a pharmaceutical company dedicated to improving the health of people around the world through provision of innovative and reliable pharmaceuticals.

Medivation, Inc. is a biopharmaceutical company focused on the rapid development of medically innovative therapies to treat serious diseases for which there are limited treatment options.