Giandomenico Roviello1, Sandra Sigala2, Shahneen Sandhu3, Alberto Bonetta4, Maria Rosa Cappelletti5, Laura Zanotti5, Alberto Bottini5, Cora N Sternberg6, Stephen B Fox7, Daniele Generali8. 1. 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. 2. Department of Molecular and Translational Medicine, University of Brescia, 25123, Brescia, Italy. 3. Department of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Australia. 4. Radiotherapy Department, Azienda Ospedaliera "Istituti Ospitalieri di Cremona", Cremona, Italy. 5. Molecular Therapy and Pharmacogenomic Unit, ASST di Cremona, Viale Concordia 1, 26100, Cremona, Italy. 6. Medical Oncology Department, San Camillo and Forlanini Hospitals, Rome, Italy. 7. Department of Pathology, Peter Mac Callum Cancer Centre, and Department of Pathology, University of Melbourne, Australia. 8. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: This study confirmed the efficacy and safety of the novel androgen receptor pathway targeted agents.
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: This study confirmed the efficacy and safety of the novel androgen receptor pathway targeted agents.
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