Role of the novel generation of androgen receptor pathway targeted agents in the management of castration-resistant prostate cancer: A literature based meta-analysis of randomized trials

BACKGROUND: Several novel androgen receptor pathway targeted agents have recently entered on to therapeutic landscape for metastatic castration-resistant prostate cancer (CRPC). We performed a meta-analysis to assess the effect of these novel androgen receptor pathway targeted agents in improving outcome of CRPC patients. METHODS: A literature-based meta-analysis of randomized controlled trials (RCTs) in accordance with the preferences for reported items in systematic reviews and meta-analyses guidelines was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology meetings were searched. The primary outcome was overall survival. The secondary end-points were time to the first symptomatic skeletal event, progression-free survival, prostatic antigen specific (PSA) response rate, time to PSA progression and safety. RESULTS: Pooled analysis from RCTs of novel androgen receptor pathway targeted agents revealed significantly increased overall survival compared with placebo or prednisone (hazard ratio [HR] for death: 0.79, 95% confidence interval [CI]: 0.71-0.87; P < 0.00001). All secondary end-points favoured the androgen receptor pathway targeted agents, although heterogeneity was high in some cases. The pooled analysis revealed that the androgen receptor pathway targeted agents significantly improved time to the first skeletal event (HR = 0.69, 95% CI: 0.63-0.75; P < 0.00001), progression-free survival (HR = 0.48, 95% CI: 0.37-0.62; P < 0.00001), time to PSA progression (HR = 0.37, 95% CI: 0.24-0.59; P < 0.0001) and PSA response rate (relative risk [RR] = 4.46, 95% CI: 2.63-7.55; P < 0.00001). The incidence of grade ≥3 adverse events was moderately higher with androgen receptor pathway targeted agents as compared with the control arms (RR = 1.11, 95% CI: 0.98-1.25; P = 0.09). CONCLUSION: This study confirmed the efficacy and safety of the novel androgen receptor pathway targeted agents