OBJECTIVES : Prostate cancer (PCa) is the sixth leading cause of cancer death and the second most common cancer in men across the world. An estimated 1.1 million men worldwide were diagnosed with prostate cancer in 2012. By 2030, PCa burden is expected to be 1.7 million new cases and 499,000 new deaths. The objective of this review is to evaluate the efficacy and safety of enzalutamide (ENZ) versus placebo in metastatic prostate cancer (mPCa) patients.

METHODS : Literature searches were conducted in MEDLINE and the Cochrane Library. In addition, references of included studies and clinicaltrials.gov were searched for relevant studies. No language or date restrictions were imposed. Study quality of included trials was assessed using the Cochrane Risk of Bias Assessment Tool. Two authors were independently selected, extracted and assessed the quality of included studies and disagreements were resolved by discussion or by consulting a third reviewer. All randomized controlled trials (RCTs) examining the efficacy and safety of enzalutamide compared to placebo in mPCa patients were included. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were objective response, any grade adverse events (AE) and the treatment discontinuation.

RESULTS : A total of 3 RCTs with 1579 patients were included. ENZ showed significantly better OS (Hazard Ratio [HR]0.668, 95% confidence interval [CI] 0.594-0.752), radiographic PFS (HR 0.291; 95%CI 0.152-0.558) and improved objective response (Risk Ratio [RR]=9.81, 95%CI 6.99-13.77) compared to placebo. There was no significant difference between the groups in terms of any grade AEs (RR=1.03, 95%CI 0.99-1.08). However, overall treatment discontinuation was lesser with ENZ (RR=0.66, 95%CI 0.55-0.78) compared to placebo. The most common adverse events in ENZ were fatigue, back pain, and hot flash.

CONCLUSIONS : Enzalutamide is associated with significant improvement in OS, PFS, and OR with tolerable side effects compared to placebo in mPCa patients.