Effectiveness and tolerability of targeted drugs for the treatment of metastatic castration-resistant prostate cancer: a network meta-analysis of randomized controlled trials.

Castration-resistant prostate cancer (CRPC) refers to prostate cancer that has progressed after initial androgen deprivation therapy (ADT). Over the years, treatment strategies for metastatic CRPC (mCRPC) have undergone considerable changes. We performed a network meta-analysis to assess the effectiveness and tolerability of targeted agents for mCRPC. We search databases including MEDLINE, EMBASE, and the Cochrane Library through Sep 5, 2017. The major effectiveness outcomes were progression-free survival (PFS) and overall survival (OS). The tolerability outcome was severe adverse events (AEs) of grade ≥ 3. Twenty-six articles assessing a total of 20,314 patients were included in this study. A random-effect analysis showed that targeted agents could significant prolong PFS in mCRPC patients (I2 = 94.3%; hazard ratio (HR): 0.74; 95% confidence interval (CI): 0.65-0.84; p < 0.001). In addition, the surface under the cumulative ranking curve (SUCRA) ranking from the network analysis showed that enzalutamide was the most effective in improving the PFS of mCRPC patients (100%), followed by abiraterone (90.1%) and tasquinimod (84.2%). Additionally, targeted agents could clearly prolong OS in mCRPC patients (I2 = 71.6%; HR: 0.91; 95% CI: 0.85-0.97; p < 0.001). Furthermore, based on SUCRA ranking, enzalutamide was the most effective in improving the OS of mCRPC patients (97.2%), followed by abiraterone (91.1%) and zibotentan (65.8%). Intetumumab was associated with the lowest incidence of severe AEs (94.9%), followed by atrasentan (85.1%) and placebo (79.3%). In patients with mCRPC, enzalutamide, abiraterone and tasquinimod can prolong PFS, and enzalutamide and abiraterone can prolong OS. Additionally, enzalutamide and abiraterone can improve both PFS and OS with a low risk of causing severe AEs.