Summary

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• Xtandi (enzalutamide) is indicated for the treatment of patients with castration-resistant prostate cancer, metastatic castration-sensitive prostate cancer, and non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high risk for metastasis.
• This summary is based on the review of 27 systematic review(s)/meta-analysis(es). ^[1-27]
• Bipolar Androgen Therapy (BAT) and Enzalutamide (Enz): In patients with castration-resistant prostate cancer (CRPC), BAT restored sensitivity to Enzalutamide, resulting in a PSA50 response rate of 57% for those who continued with AR-targeted therapy, including Enz.
• Combination with Androgen-Deprivation Therapy (ADT): In docetaxel-naive and low-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients, Enzalutamide combined with ADT significantly improved overall survival, with hazard ratios of 0.429 and 0.533, respectively.
• New Generation Anti-Androgens: The addition of new-generation anti-androgens to ADT improved overall survival (HR 0.66) and failure-free survival (HR 0.43) in prostate cancer patients.
• Direct Comparisons: Enzalutamide demonstrated superior radiographic progression-free survival (HR 0.516) and time to PSA progression (HR 0.365) compared to abiraterone in prostate cancer patients.
• BAT followed by Enzalutamide resulted in a 14% incidence of grade ≥3 adverse events (AEs).
• The combination of androgen-deprivation therapy (ADT) with new-generation anti-androgens, including Enzalutamide, increased the odds of grade ≥3 AEs with an odds ratio (OR) of 1.40.
• Enzalutamide treatment showed a higher incidence of hypertension and fatigue compared to abiraterone, which was associated with higher rates of hypokalemia and fluid retention.
• Enzalutamide has shown effectiveness and consistent safety across various specific populations, including better overall survival in docetaxel-naive and low-volume disease, benefits for Asian patients with advanced prostate cancer, and improved outcomes in BRCA1/2 mutation-positive patients. However, it requires careful cardiovascular monitoring due to an increased risk of hypertension and fatigue, particularly in patients with an elevated neutrophil-to-lymphocyte ratio, which is associated with worse survival outcomes in mCRPC.