A systematic review and meta-analysis on overall survival, failure-free survival and safety outcomes in patients with metastatic hormone-sensitive prostate cancer treated with new anti-androgens.

Abstract

Objective Androgen-deprivation therapy (ADT) combined with new antiandrogens have shown to improve the outcomes of patients with hormone-sensitive metastatic prostate cancer. This systematic review and meta-analysis aim to compare the efficacy and toxicity of these agents in this specific scenario. Methods Randomized clinical trials (RCT) were identified after systematic searching of databases. A random-effect model was used to determine the pooled hazard ratio (HR) for overall survival (OS) and failure-free survival according to the inverse-variance method. The Mantel-Haenszel method was used to calculate the pooled odds ratio (OR) for treatment-related adverse events (AEs) grade 3 or higher. Heterogeneity was determined using the Tau2 and I 2 statistics. Results Seven trials were included in this meta-analysis (n = 7544). The addition of ADT plus new-generation anti-androgens, specifically: abiraterone, apalutamide, darolutamide or enzalutamide was associated with improved OS (pooled HR, 0.66; 95% CI, 0.61–0.71; P < 0.00001) with no significant heterogeneity detected among trials. (Tau2 = 0; I 2 = 0%; P = 0.88). Failure-free survival was significantly longer in the combination-therapy group than in the control group (pooled HR, 0.43; 95% CI, 0.39–0.47; P < 0.00001) This effect was consistent among trials (Tau2 = 0; I 2 = 27%; P = 0.22). The overall OR of AEs grade 3 or higher was significantly increased with the use of the combination therapy (pooled OR, 1.40; 95% CI, 1.13–1.74; P = 0.002), with significant heterogeneity among trials (Tau2 = 0.07; I 2 = 82%; P < 0.0001). Conclusion: The addition of either abiraterone, apalutamide, darolutamide or enzalutamide to ADT improves OS and failure-free survival in hormone-sensitive metastatic prostate cancer, albeit an increase in AEs.