Published online Aug 10, 2015. doi: 10.5306/wjco.v6.i4.64
Peer-review started: October 28, 2014
First decision: December 26, 2014
Revised: May 18, 2015
Accepted: June 4, 2015
Article in press: June 8, 2015
Published online: August 10, 2015
Processing time: 294 Days and 17.2 Hours
AIM: To study the efficacy and safety of abiraterone in patients with and without prior chemotherapy.
METHODS: The databases including PubMed and abstracts presented at the American Society of Clinical Oncology meetings up to April 2014 were systematically searched. Eligible studies included randomized controlled trials (RCTs) in which abiraterone plus prednisone was compared to placebo plus prednisone in metastatic castration-resistant prostate cancer (CRPC) patients. The summary incidence, relative risk, hazard ratio and 95%CI were calculated using random or fixed-effects models. Heterogeneity test was performed to test between-study differences in efficacy and toxicity.
RESULTS: A total of two phase III RCTs were included in our analysis, with metastatic CPRC patients before (n = 1088) and after chemotherapy (n = 1195). Prior chemotherapy did not significantly alter the effect of abiraterone on overall survival (P = 0.92) and prostate-specific antigen (PSA) progression-free survival (P = 0.13), but reduced its effect on radiographic-progression-free survival (P = 0.04), objective response rate (P < 0.001), and PSA response rate (P < 0.001). Prior chemotherapy significantly increased the specific risk of fluid retention and edema (P < 0.001) and hypokalemia (P < 0.001), but decreased the risk of all-grade hypertension (P < 0.001) attributable to abiraterone. There was no significant difference of cardiac disorders associated with abiraterone between the two settings (P = 0.58).
CONCLUSION: Prior chemotherapy may reduce the effectiveness of abiraterone in patients with metastatic CRPC.
Core tip: Our meta-analysis has demonstrated that pre-chemotherapy may affect the efficacy and toxicity of abiraterone treatment in patients with metastatic castration-resistant prostate cancer. Abiraterone was associated with significantly increased radiographic-progression-free survival, objective response rate, and prostate-specific antigen response rate in the pre-chemotherapy setting when compared to the post-chemotherapy setting. In addition, abiraterone in the pre-chemotherapy setting had a significant lower risk of all-grade fluid retention and edema (P < 0.001), and hypokalemia (P < 0.001), but had a higher risk of all-grade hypertension (P < 0.001) when compared to post-chemotherapy.