Advances in therapies have led to the approval of six therapeutic agents since 
2004, each demonstrating overall survival benefit in randomized studies, and 
these have significantly improved the outlook for men facing metastatic 
castration-resistant prostate cancer (CRPC). More recently, efforts have been 
directed at trying to effect change at earlier phases of the disease. 
Apalutamide (ARN-509), a second-generation androgen receptor antagonist, 
recently received approval in the nonmetastatic (M0) CRPC space. Similar to 
enzalutamide, apalutamide inhibits the binding of androgen to androgen receptor 
(AR), nuclear translocation of the androgen-AR complex, and binding of AR 
transcription complex to DNA-binding sites and transcription elements. Phase I 
and II trial experience demonstrates the safety and tolerability of apalutamide, 
as well as its efficacy in effecting prostate-specific antigen response and 
radiographic-free survival in CRPC. US Food and Drug Administration approval in 
M0 CRPC was granted following positive results from the phase III SPARTAN study, 
where apalutamide demonstrated significant improvements in metastasis-free 
survival and time to symptomatic progression as compared to placebo.