STRIVE Trial Suggests Enzalutamide May Have Benefits Over Bicalutamide

Enzalutamide may provide a statistically significant increase in progression-free survival (PFS) compared to bicalutamide in men with nonmetastatic or metastatic castration-resistant prostate cancer. New results from the Phase II STRIVE trial comparing enzalutamide with bicalutamide demonstrated that the median PFS was 19.4 months in men treated with enzalutamide (Xtandi) compared with 5.7 months in men treated with bicalutamide (Casodex).

The Phase II STRIVE (Safety and Efficacy Study of Enzalutamide Versus Bicalutamide in Men with Prostate Cancer) trial included 396 castration-resistant prostate cancer patients (257 patients with metastatic disease and 139 patients with nonmetastatic prostate cancer) whose disease progressed despite treatment with a luteinizing hormone-releasing hormone (LHRH) analogue therapy or following surgical castration. The study achieved its primary endpoint, and demonstrated a statistically significant increase in PFS for enzalutamide compared with bicalutamide (HR = 0.24).

Enzalutamide is an androgen receptor inhibitor that acts on three different steps in the androgen receptor signaling pathway, and it is approved by the US Food and Drug Administration (FDA) for the treatment of men with metastatic castration-resistant prostate cancer (CRPC).

The median time on treatment in the STRIVE trial was 14.7 months in the enzalutamide group compared to 8.4 months in the bicalutamide group, according to the latest results announced on April 2, 2015 by Astellas Pharma, Inc.

The company reported that the serious adverse event rates were slightly higher in the enzalutamide group (29.4% of enzalutamide-treated patients compared to 28.3% of bicalutamide-treated patients). Grade 3 or higher cardiac adverse events were also slightly higher (5.1% of enzalutamide-treated patients compared to 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 in the enzalutamide-treated vs bicalutamide-treated patients included fatigue, back pain, flushing, hypertension, dizziness, and decreased appetite. These were all considered to be consistent with the known safety profile of enzalutamide. 

Co-principal investigator of the STRIVE study David Penson, MD, who is the Director of the Center for Surgical Quality and Outcomes Research and Chair of the Department of Urologic Surgery at Vanderbilt University Medical Center, Nashville, Tenn., said these results demonstrate the potential for enzalutamide to provide a longer duration of disease control compared with bicalutamide in the studied patient population.

The STRIVE study is the second of two head-to-head studies of enzalutamide compared to bicalutamide. The first study was TERRAIN: A randomized, double-blinded, phase II study comparing MDV3100 with bicalutamide in men with metastatic castrate-resistant prostate cancer, and it included 375 patients in North America and Europe. The TERRAIN study also achieved its primary endpoint, suggesting a statistically significant increase in PFS for enzalutamide compared to bicalutamide (HR = 0.44).

Additional results from the STRIVE trial--including the secondary endpoints and safety data--will be submitted for presentation at medical conferences later this year.