Perspectives on Treatment of Metastatic Castration-Resistant Prostate Cancer

Abstract

The arrival of several new agents-cabazitaxel, abiraterone acetate, enzalutamide, and radium-223-is changing the treatment options and management of patients with metastatic castration-resistant prostate cancer (mCRPC). Many other novel agents are also being investigated. As new drugs become approved, new treatment strategies and markers to best select which patients will best respond to which drug are needed. This review article is a summary of a European Treatment Practices Meeting, which was convened to discuss these latest data on novel agents and current treatment strategies in the mCRPC setting. The Oncologist 2013;18:558 -567 Implications for Practice: With so many novel agents available to treat patients with metastatic castration-resistant prostate cancer (mCRPC), a better understanding of factors to consider when assessing the clinical utility of treatment options for patients is needed. This review article discusses treatment strategies for mCRPC in the first-and second-line setting, and highlights the role of clinical markers, patient history, and assessing fitness for treatment when making treatment decisions. Prostate cancer is a heterogeneous disease, therefore, treatment must consider the characteristics of the disease as it manifests in an individual patient. In addition, assessments of patient response to treatment should reflect the mechanism of the drug. Further study is needed to identify predictive biomarkers to indicate patient response to novel agents.

Alterations of androgen receptor-regulated enhancer RNAs (eRNAs) contribute to enzalutamide resistance in castration-resistant prostate cancer

“…Unfortunately, 2–3 years after treatment, CRPC develops in most patients [37, 38]. CRPC is associated with poor prognosis [39], with the median survival time varying from 9 to 30 months and metastases in over 84% of CRPC patients which reduces the mean survival to around 14 months [40]. As a new-generation hormonal therapy, enzalutamide offers an alternative in the treatment for patients with CRPC.…”

Development of enzalutamide for metastatic castration‐resistant prostate cancer

“…The current standard of care for advanced prostate cancer is androgen deprivation therapy (ADT), achieved through orchiectomy, administration of luteinizing hormone–releasing hormone (LHRH) analogs with or without an antiandrogen, or LHRH antagonists, resulting in remission of disease in approximately 90% of patients . However, after 5 years, approximately 10–20% of patients undergo disease progression signaled by a rise in prostate‐specific antigen (PSA) despite continuous hormonal manipulation and castrate testosterone levels . This disease state, known as castration‐resistant prostate cancer (CRPC), is associated with poor prognosis, with a mean survival time of 9–13 months and deterioration in quality of life …”

“…However, after 5 years, approximately 10–20% of patients undergo disease progression signaled by a rise in prostate‐specific antigen (PSA) despite continuous hormonal manipulation and castrate testosterone levels . This disease state, known as castration‐resistant prostate cancer (CRPC), is associated with poor prognosis, with a mean survival time of 9–13 months and deterioration in quality of life …”

Enzalutamide in European and North American men participating in the AFFIRM trial

“…Metastatic castration-resistant prostate cancer (mCRPC), characterised by disease progression after surgical or medical castration, remains a chronic disease with a poor prognosis 1 . In vitro, in vivo and profiling studies of human prostate cancers show that continued activation of signalling through the androgen receptor (AR) pathway is frequent and that the disease remains sensitive to further hormonal treatments 2 – 4 .…”