ESA Approximately 15% to 25% of patients with CRPC do not respond to first-line treatment with either abiraterone (Zytiga, Janssen) or enzalutamide (Xtandi, Astellas/Medivation), meaning that their prostate-specific antigen (PSA) values do not decrease or their tumors do not regress. The other 75% to 85% of patients respond to abiraterone or enzalutamide initially, but a subsequent PSA increase or tumor progression occurs in nearly all of them with time. In the first-line CRPC setting, resistance typically develops after 9 to 15 months of treatment with either agent. What is interesting is that patients who receive enzalutamide or abiraterone as first-line therapy and subsequently become resistant have only a 15% to 30% rate of response to the alternative agent as second-line CRPC treatment. That finding clearly shows that cross-resistance occurs between enzalutamide and abiraterone. Resistance to second-line therapy takes approximately 3 to 6 months to develop, so the duration of benefit of second-line CRPC therapy is decreased by at least 50% compared with that of first-line therapy.