Abiraterone for Treatment of Metastatic Castration-resistant Prostate Cancer: a Systematic Review and Meta-analysis

Introduction: Although most prostate cancers initially respond to castration with luteinizing hormonereleasinganalogues or bilateral orchiectomy, progression eventually occurs. Based on the exciting results ofseveral randomized controlled trials (RCTs), it seems that patients with metastatic castration-resistant prostatecancer (mCRPC) might benefit more from treatment withabiraterone. Therefore we conducted a systematicreview to evaluate the efficacy and toxicity of abiraterone in the treatment of mCRPC.
Methods: Literaturewas searched from Embase, PubMed, Web of Science, and Cochrane Library up to July, 2013. Quality of thestudy was evaluated according to the Cochrane’s risk of bias of randomized controlled trial (RCT) tool, then theGrading of Recommendations Assessment, Development and Evaluation (GRADE) System was used to rate thelevel of evidence. Stata 12.0 was used for statistical analysis. Summary data from RCTs comparing abirateroneplus prednisone versus placebo plus prednisone for mCRPC were meta-analyzed. Pooled hazard ratios (HRs)for overall survival (OS), radiographic progression-free survival (RPFS) and time to PSA progression (TTPP);Pooled risk ratios (RR) for PSA response rate, objective response rate and adverse event were calculated.
Results:Ten trials were included in the systematic review; Data of 2,283 patients (1,343 abiraterone; 940 placebo) fromtwo phase 3 trials: COU-AA-301 and COU-AA-302 were meta-analyzed. Compared with placebo, abirateronesignificantly prolonged OS (HR, 0.74; 95% confidence interval [CI], 0.66 to 0.84), RPFS (HR, 0.59; 95% CI,0.48 to 0.74) and time to PSA progression (HR, 0.55; 95% CI, 0.43 to 0.70); it also significantly increased PSAresponse rate (RR, 3.63; 95% CI, 1.72 to 7.65) and objective response rate (RR, 3.05; 95% CI, 1.51 to 6.15). Thismeta-analysis suggested that the adverse events caused by abiraterone are acceptable and can be controlled.Conclutios: Abiraterone significantly prolonged OS, RPFS and time to progression patients with mCRPC,regardless of prior chemotherapy or whether chemotherapy-naïve, and no unexpected toxicity was evident.Abiraterone can serve as a new standard therapy for mCRPC.