title: Role of the novel generation of androgen receptor pathway targeted agents in the management of castration-resistant prostate cancer: A literature based meta-analysis of randomized trials.
abstract: Several novel androgen receptor pathway targeted agents have recently entered on to therapeutic landscape for metastatic castration-resistant prostate cancer (CRPC). We performed a meta-analysis to assess the effect of these novel androgen receptor pathway targeted agents in improving outcome of CRPC patients.
  
  
  
  A literature-based meta-analysis of randomized controlled trials (RCTs) in accordance with the preferences for reported items in systematic reviews and meta-analyses guidelines was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology meetings were searched. The primary outcome was overall survival. The secondary end-points were time to the first symptomatic skeletal event, progression-free survival, prostatic antigen specific (PSA) response rate, time to PSA progression and safety.
  
  
  
  Pooled analysis from RCTs of novel androgen receptor pathway targeted agents revealed significantly increased overall survival compared with placebo or prednisone (hazard ratio [HR] for death: 0.79, 95% confidence interval [CI]: 0.71-0.87; P < 0.00001). All secondary end-points favoured the androgen receptor pathway targeted agents, although heterogeneity was high in some cases. The pooled analysis revealed that the androgen receptor pathway targeted agents significantly improved time to the first skeletal event (HR = 0.69, 95% CI: 0.63-0.75; P < 0.00001), progression-free survival (HR = 0.48, 95% CI: 0.37-0.62; P < 0.00001), time to PSA progression (HR = 0.37, 95% CI: 0.24-0.59; P < 0.0001) and PSA response rate (relative risk [RR] = 4.46, 95% CI: 2.63-7.55; P < 0.00001). The incidence of grade ≥3 adverse events was moderately higher with androgen receptor pathway targeted agents as compared with the control arms (RR = 1.11, 95% CI: 0.98-1.25; P = 0.09).
  
  
  
  This study confirmed the efficacy and safety of the novel androgen receptor pathway targeted agents.
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, 25123, Brescia, Italy; Molecular Therapy and Pharmacogenomic Unit, ASST di Cremona, Viale Concordia 1, 26100, Cremona, Italy. Electronic address: giandomenicoroviello@gmail.com.
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Roviello
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, 25123, Brescia, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sigala
authors.affiliation: Department of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Australia.
authors.forename: Shahneen
authors.initials: S
authors.lastname: Sandhu
authors.affiliation: Radiotherapy Department, Azienda Ospedaliera "Istituti Ospitalieri di Cremona", Cremona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bonetta
authors.affiliation: Molecular Therapy and Pharmacogenomic Unit, ASST di Cremona, Viale Concordia 1, 26100, Cremona, Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Cappelletti
authors.affiliation: Molecular Therapy and Pharmacogenomic Unit, ASST di Cremona, Viale Concordia 1, 26100, Cremona, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zanotti
authors.affiliation: Molecular Therapy and Pharmacogenomic Unit, ASST di Cremona, Viale Concordia 1, 26100, Cremona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bottini
authors.affiliation: Medical Oncology Department, San Camillo and Forlanini Hospitals, Rome, Italy.
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.affiliation: Department of Pathology, Peter Mac Callum Cancer Centre, and Department of Pathology, University of Melbourne, Australia.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Fox
authors.affiliation: Molecular Therapy and Pharmacogenomic Unit, ASST di Cremona, Viale Concordia 1, 26100, Cremona, Italy; Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129, Trieste, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Generali
mesh_terms: D059002:Androgen Receptor Antagonists / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods*; D016016:Proportional Hazards Models; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents
keywords: Abiraterone acetate; Enzalutamide; Orteronel; Prostate cancer