Enzalutamide has modest clinical activity in men with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel and abiraterone acetate, according to the largest study of this therapeutic approach to date. Of 69 patients, 21% experienced a maximum PSA decline of ≥50%, and enzalutamide was generally well tolerated in this cohort. PSA response to docetaxel and abiraterone did not predict PSA response to enzalutamide.