The “Artificial” Docetaxel Space: The Evolving Treatment Paradigm of Metastatic Castration-Resistant Prostate Cancer

Abstract

Over the past few years, our repertoire of therapeutic options in metastatic castration-resistant prostate cancer (mCRPC) has expanded, with six novel therapies having a proven survival benefit. These include the initially developed docetaxel >10 yr ago, followed by sipuleucel-T, abiraterone, cabazitaxel, enzalutamide, and radium-223. Beyond this clear progress, new challenges emerge now on how to optimize their use. Owing to development timing, a nonbiologic/artificial distinction of preand postchemotherapy now exists in the mCRPC setting. However, the optimal sequencing, the potential synergistic activity when used in combination, or the use of biomarkers to optimally select treatment for individual patients is unknown for all these new treatment approaches. The challenge that lies ahead is positioning these agents in an increasingly complex CRPC treatment paradigm, as well as bringing these agents into the early CRPC setting or even into the hormone-sensitive arena. When hormonal maneuvers were believed to be exhausted, a new generation of molecules has shown that androgen receptor (AR) signaling still remains an important driver of CRPC. Abiraterone and enzalutamide are both oral therapies that target the AR pathway. Abiraterone acetate is inhibits androgen synthesis by selectively inhibiting CYP17 and has been approved both in the preand postchemotherapy space (Abiraterone Acetate in Castration-Resistant Prostate Cancer Previously Treated with Docetaxel-Based Chemotherapy [COU-AA-301] and Abiraterone Acetate in Asymptomatic or Mildly Symptomatic Patients with Metastatic Castration-Resistant Prostate Cancer [COU-AA-302] clinical trials).