1. Department of Urology, Sun Yat-Sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China;
2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China;
3. Department of Interventional oncology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
4. Academic Urology Unit, University of Aberdeen, Cornhill Road, Aberdeen, UK.
*These authors (Changhao Chen, Hao Huang and Yue Zhao) contributed equally to this study.
Background: Most patients receiving docetaxel-based chemotherapy for castration resistant prostate cancer (CRPC) will eventually progress, and the optimal interventions for these patients are controversial. The objective of our study is to evaluate the clinical efficacy and safety of pharmacological interventions for CRPC patients progressing after docetaxel-based chemotherapy.
Methods: A systematic review and Bayesian network meta-analysis of the literature was carried out according to standard methods. Major electronic databases including PubMed, Web of Science and Embase were searched until Jan 2017. Hazard ratios (HRs) and odds ratios (ORs) with corresponding 95% credible intervals (CrIs) were used to estimate the association.
Results: 17 Randomized Controlled Trials (RCTs) comprising 14 different interventions with 12347 patients were enrolled. Compared with control arms, Abiraterone Acetate (HR: 0.70, 95%CrI: 0.63-0.79), Cabazitaxel (HR: 0.70, 95%CrI: 0.51-0.95) and Enzalutamide (HR: 0.63, 95%CrI: 0.53-0.75) presented similar benefits in term of OS. Enzalutamide showed superiority over PFS and PSA response with a highest probability to rank 1. Moreover, sensitivity analysis showed that Abiraterone Acetate (HR: 0.71, 95%CrI: 0.63-0.78) exhibited the most efficacious intervention of being rank 1 in term of OS compared with control arms, followed by Cabazitaxel and Cetuximab. On the other hand, Abiraterone Acetate (OR: 0.86, 95%CrI: 0.35-2.03) presented no significant toxicities compared with control arms.
Conclusions: Our results demonstrated that Abiraterone Acetate might be the optimal intervention for CRPC patients after docetaxel failure with acceptable tolerability. Future well-designed RCTs and systematic reviews are needed to validate these findings.
Keywords: Castration resistant prostate cancer, Pharmacological Interventions, Docetaxel-based Chemotherapy, Bayesian network meta-analysis, Abiraterone Acetate, Enzalutamide