Second-line treatment options in metastatic castration-resistant prostate cancer: A comparison of key trials with recently approved agents

Abstract

Standard first-line treatment for metastatic castration-resistant prostate cancer (mCRPC) is docetaxel plus prednisone; however, patients will usually experience disease progression during or after docetaxel treatment due to inherent or acquired resistance. Before 2010, second-line options for mCRPC were limited. However, cabazitaxel, abiraterone acetate and enzalutamide have since been approved for patients with mCRPC whose disease has progressed during or after receiving docetaxel, based on the Phase III trials TROPIC, COU-AA-301 and AFFIRM. In all three trials, an overall survival benefit (primary endpoint) was seen in the experimental arm compared with the control arm: 15.1 vs. 12.7months for cabazitaxel plus prednisone compared with mitoxantrone plus prednisone in TROPIC (hazard ratio [HR] 0.70; P<0.0001); 14.8 vs. 10.9months for abiraterone acetateplus prednisone compared with placebo plus prednisone in COU-AA-301 (HR 0.65; P<0.001); and 18.4 vs. 13.6months for enzalutamide compared with placebo alone in AFFIRM (0.63; P<0.001). However, differences in patient populations, comparators, and selection and/or definition of secondary endpoints make it difficult to draw direct cross-trial comparisons. Radium-223 dichloride has also been approved for patients with mCRPC with metastases to bone but not other organs. To date, no comparative trials or sequencing studies with newer agents have been performed. Without such data, treatment decisions must be based on evaluation of the existing evidence. This commentary compares and contrasts study designs and key data from each of these Phase III trials, and also discusses recent and ongoing clinical trials with new agents in the first- and second-line settings in mCRPC.

Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization

“…At this stage, second-line endocrine therapy and chemotherapy should be administered (3). Docetaxel (DTX) is a clinically approved drug for the treatment of various metastatic CRPCs (4). The majority of metastatic prostate cancers can be effectively treated with DTX (5).…”

Antiproliferative Mechanism of Action of the Novel Taxane Cabazitaxel as Compared with the Parent Compound Docetaxel in MCF7 Breast Cancer Cells

“…Cabazitaxel (Jevtana) is a novel third-generation semisynthetic analog of docetaxel (8,(10)(11)(12). Structurally, cabazitaxel and docetaxel are very similar with the exception of 2 methoxy side chains in cabazitaxel that substitute for hydroxyl groups in docetaxel (Fig.…”

Translating Clinical Evidence-Based Medicine into the Real World: Single-Center Experience with Cabazitaxel in Metastatic Prostate Cancer Patients

“…AA or enzatulamide may be preferable to chemotherapy both in patients with asymptomatic disease and in patients with comorbidities or factors predisposing to poor tolerance of chemotherapy. On the other hand, for patients with rapidly progressing disease or visceral metastases, or patients with a poor response to initial androgen deprivation therapy, the use of chemotherapy may be preferred [17,18]. Age should not be a limiting factor as efficacy has been reported irrespective of the overall health status and tumor response even for very elderly patients [19].…”