New Agents for the Management of Castration-Resistant Prostate Cancer

Robert J Cersosimo PharmD BCOP

Disclosures

The Annals of Pharmacotherapy. 2012;46(11):1518-1528. 

In This Article

Abstract and Introduction

Abstract

Objective: To review the activity of 3 new agents approved for the management of advanced castration-resistant prostate cancer (CRPC): sipuleucel-T, cabazitaxel, and abiraterone acetate.
Data Sources: Literature was accessed through MEDLINE (1977-June 2012) and abstracts from the American Society of Clinical Oncology (2000–2012) using the terms castration-resistant and hormone-refractory prostate cancer, sipuleucel-T, cabazitaxel, abiraterone, Provenge, Jevtana, and Zytiga. Reference citations from publications identified were also reviewed.
Study Selection and Data Extraction: Articles identified from the data sources in English on human subjects were evaluated.
Data Synthesis: Options for patients with CRPC have been limited, with little to offer those who failed or could not tolerate docetaxel-based therapy. Three new drugs, with very different mechanisms of action, have changed that and will undoubtedly change the treatment paradigm for these patients. Each agent has demonstrated an impact on patient survival. Sipuleucel-T, the first immunotherapy approved for treatment of CRPC, improved median overall survival by 4.1 months and reduced the risk of death by 22% in a placebo-controlled trial of asymptomatic patients. Sipuleucel-T can be administered prior to docetaxel-based therapy. Cabazitaxel, a taxane chemotherapy agent, improved median overall survival by 2.4 months and reduced the risk of death by 30% in a Phase 3 trial of patients whose cancer progressed during or after docetaxel-based therapy. Abiraterone acetate, a hormonal therapy, improved median overall survival by 3.9 months and reduced the risk of death by 35% in patients with relapse during or after docetaxel-based therapy.
Conclusions: The advent of new agents for the management of advanced CRPC has increased the choices for patients whose options were limited. Additional experience will determine the optimal sequencing of these agents, their roles in combination therapy, and their activity in patients with earlier disease.

Introduction

Prostate cancer is the most commonly diagnosed malignancy in American men. The American Cancer Society estimates that 241,740 men will be diagnosed with prostate cancer in 2012, accounting for 29% of newly diagnosed cancers.[1] Approximately 28,170 men will die from this disease in 2012. At diagnosis, approximately 4% of patients have advanced disease.[1] Using American Cancer Society figures, approximately 9670 men will be diagnosed with advanced disease annually. Androgen deprivation therapy is the most common initial treatment for men with advanced disease. First-line therapy includes luteinizing hormone-releasing hormone (LHRH) agonists, antiandrogens, and orchiectomy. Most men treated with androgen deprivation therapy respond, but with time most patients develop hormone-refractory or castration-resistant prostate cancer (CRPC). A review characterizing the CRPC population revealed that 10–20% of patients develop castration-resistant disease within 5 years of follow-up.[2] The most commonly used initial treatment for CRPC is chemotherapy with docetaxel and prednisone. In a pivotal Phase 3 randomized study of 1006 men with metastatic CRPC, the median overall survival with 3-week docetaxel plus prednisone was 19.2 months, versus 16.3 months with mitoxantrone plus prednisone (p = 0.004), an advantage of about 3 months.[3,4] This docetaxel regimen has become the standard of care for men with CRPC and is endorsed by the American Society of Clinical Oncology and the National Comprehensive Cancer Network (NCCN).[5,6]

Three new agents have been approved for management of CRPC: sipuleucel-T (approved in April 2010), cabazitaxel (June 2010), and abiraterone (April 2011). These agents are the focus of this review. A comparison of agents currently approved for treatment of patients with metastatic CRPC is presented in Table 1.[3,4,7–10]

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