Comparing the clinical efficacy of abiraterone acetate, enzalutamide, and orteronel in patients with metastatic castration-resistant prostate cancer by performing a network meta-analysis of eight randomized controlled trials
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Minyong Kang1, Chang Wook Jeong2, Cheol Kwak2, Ja Hyeon Ku2,* and Hyeon Hoe Kim2,*
1Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
2Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea
*These authors contributed equally to this work
Ja Hyeon Ku, email: email@example.com
Hyeon Hoe Kim, email: firstname.lastname@example.org
Keywords: castration-resistant prostate cancer, androgen receptor signaling, targeted drug, systematic review, network meta-analysis
Received: February 27, 2017 Accepted: April 25, 2017 Published: May 10, 2017
Various novel androgen receptor (AR) targeting drugs have been developed recently and have shown beneficial effects on survival in patients with metastatic castration-resistant prostate cancer (mCRPC). However, no consensus has been reached regarding which of these agents provides the most favorable oncological outcomes. Here, we aimed to compare the efficacy of novel AR-targeted agents by performing a network meta-analysis of randomized controlled trials (RCTs). We included eight RCTs for men with mCRPC treated with one of the AR targeting agents: abiraterone acetate, enzalutamide, or orteronel. The primary endpoint was overall survival (OS), while the secondary endpoints were progression-free survival (PFS), prostate-specific antigen (PSA) responsiveness, time to PSA progression, time to first skeletal-related events (SRE), and adverse events (AEs). Pairwise meta-analysis and network meta-analysis were conducted to obtain direct and indirect evidence, respectively. Notably, enzalutamide and abiraterone were significantly associated with improved OS compared with control arms. Enzalutamide was ranked as the most efficacious agent for improving OS (hazard ratio [HR] = 0.71), and abiraterone appeared to be the second-most efficacious drug for this purpose (HR = 0.78). Enzalutamide improved PFS in comparison with control groups (HR = 0.36), but abiraterone and orteronel were not significantly associated with PFS improvements. Enzalutamide (HR = 0.20) and abiraterone (HR = 0.56) were significantly associated with prolonged times to PSA progression as compared with control groups. However, only orteronel was associated with an increased risk of AEs as compared with control groups. In summary, our study can help to guide treatment selection, especially because AR-targeted agents have not been compared directly in head-to-head trials.
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