Management of Castration-resistant Prostate Cancer: Second-line Therapies

Until 2010, the only approved life-prolonging treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) was docetaxel. Since 2010, abiraterone acetate, enzalutamide, and cabazitaxel have demonstrated overall survival (OS) benefits in the postdocetaxel setting. The COU-AA-301 trial showed an OS advantage with abiraterone acetate plus prednisone compared with placebo plus prednisone. A superior OS was also seen in the AFFIRM trial that compared enzalutamide with placebo and in the TROPIC trial that compared cabazitaxel plus prednisone with mitoxantrone plus prednisone Radium-223 dichloride has also been approved based on the ALSYMPCA trial for symptomatic patients with castration-resistant prostate cancer (CRPC) metastatic to bone only. Optimal sequencing of approved therapies remains controversial. In this chapter, we will review the approved agents in second-line treatment of CRPC and discuss the sequencing options. This review contains 4 figures, 5 tables, and 57 references. Key Words: abiraterone acetate, cabazitaxel, castration-resistant, docetaxel, enzalutamide, MDV 3100, prostatic neoplasms, radium-223 dichloride, sequencing of therapy