257 Background: Five new agents with diverse mechanisms of action have been shown to improve overall survival for patients with advanced castration-refractory prostate cancer (CRPC). Because of a heterogeneity in cancer growth and proliferation, it is not clear whether these agents are effective in patients with rapid progressive disease. Therefore, we conducted a systematic review and meta-analysis of published randomized controlled clinical trials (RCTs) to assess the effect of these new agents on three month progression and mortality. Methods: Databases from PUBMED, the Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until June, 2013 were searched to identify relevant studies. Early progression was defined as progressive disease or death at three months after the initiation of clinical trial. Eligible studies included prospective RCTs in which a new agent was compared to a control in metastatic CRPC patients. Summary incidences of three month progression or mortality, relative risk (RR), and 95% confidence interval (CI) were calculated based on the heterogeneity of included studies. Results: A total of 5,895 patients (new agents: 3,623, control: 2,272) with CRPC from seven RCTs were included for analysis. The new therapy significantly reduced the risk of mortality in the overall patient population (HR=0.69, 95% CI: 0.64-0.74) without significant variation among different agents (P=0.82). The new therapy also reduced the risk of three month mortality (RR=0.76, 95% CI: 0.60-0.97, P=0.027). However, significant risk reduction was only seen for enzalutamide (RR=0.54, 95% CI: 0.31-0.94; P=0.03). In addition, the new therapy reduced the risk of three month progression (RR=0.61, 95% CI: 0.46-0.81, P=0.001). The risk varied among these agents (P<0.001), with significant risk reduction seen for enzalutamide (RR=0.47, 95% CI: 0.21-0.54), abiraterone (RR=0.57, 95%CI: 0.35-0.97), and cabazitaxel (RR=0.80, 95% CI: 0.72-0.89), but not for Sipuleucel-T (RR=1.10, 95% CI: 0.21-5.76). Conclusions: The new agents may have a differential impact on the outcome of CRPC with rapid progression.