PMID- 34308608 OWN - NLM STAT- MEDLINE DCOM- 20220525 LR - 20220623 IS - 2724-6442 (Electronic) IS - 2724-6051 (Linking) VI - 74 IP - 3 DP - 2022 Jun TI - Androgen receptor axis-targeted agents for non-metastatic castration-resistant prostate cancer impact on overall survival and safety profile. PG - 292-301 LID - 10.23736/S2724-6051.21.04431-1 [doi] AB - INTRODUCTION: The management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with the development of androgen receptor axis-targeted (ARAT) agents. The updated results with final overall survival (OS) data of the phase III PROSPER, SPARTAN, and ARAMIS trials have recently been reported. Therefore, we performed an updated meta-analysis and network meta-analysis to indirectly compare the efficacy and safety of currently available treatments. EVIDENCE ACQUISITION: Multiple databases were searched for articles published before January 2021. Studies that compared OS and adverse events (AEs) in patients with nmCRPC were considered eligible. EVIDENCE SYNTHESIS: Three studies (N.=4117) met our eligibility criteria. Formal network meta-analyses were conducted. ARAT agent is associated with significantly longer OS compared to placebo (pooled hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.65-0.83, P<0.001), with similar results shown for patients with both N1 and N0 disease (pooled HR 0.61 and pooled HR 0.76, respectively). In the network meta-analysis, apalutamide, darolutamide, and enzalutamide were more effective than placebo, with similar efficacies in terms of OS. For AEs (including any AEs, grade 3 or grade 4 AEs, grade 5 AEs, serious AEs, and AEs leading to treatment discontinuation), darolutamide was shown to be likely well tolerated. Quality of Life was preserved in treatment arms irrespective of the drug. CONCLUSIONS: All three ARAT agents are efficacious options for the treatment of nmCRPC, whereas darolutamide appears to have the most favorable tolerability profile. These findings may facilitate individualized treatment strategies and inform future direct comparative trials. FAU - Mori, Keiichiro AU - Mori K AD - Department of Urology, Medical University of Vienna, Vienna, Austria - keiichiro.mori@meduniwien.ac.at. AD - School of Medicine, Department of Urology, Jikei University, Tokyo, Japan - keiichiro.mori@meduniwien.ac.at. FAU - Quhal, Fahad AU - Quhal F AD - Department of Urology, Medical University of Vienna, Vienna, Austria. AD - Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia. FAU - Katayama, Satoshi AU - Katayama S AD - Department of Urology, Medical University of Vienna, Vienna, Austria. AD - Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Urology, Okayama University, Okayama, Japan. FAU - Mostafaei, Hadi AU - Mostafaei H AD - Department of Urology, Medical University of Vienna, Vienna, Austria. AD - Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. FAU - Laukhtina, Ekaterina AU - Laukhtina E AD - Department of Urology, Medical University of Vienna, Vienna, Austria. AD - Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. FAU - Schuettfort, Victor M AU - Schuettfort VM AD - Department of Urology, Medical University of Vienna, Vienna, Austria. AD - Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Sari Motlagh, Reza AU - Sari Motlagh R AD - Department of Urology, Medical University of Vienna, Vienna, Austria. AD - Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Grossmann, Nico C AU - Grossmann NC AD - Department of Urology, Medical University of Vienna, Vienna, Austria. AD - Department of Urology, University Hospital Zurich, Zurich, Switzerland. FAU - Rajwa, Pawel AU - Rajwa P AD - Department of Urology, Medical University of Vienna, Vienna, Austria. AD - Department of Urology, Medical University of Silesia, Zabrze, Poland. FAU - Ploussard, Guillaume AU - Ploussard G AD - Department of Urology, La Croix du Sud Hospital, Quint Fonsegrives, France. FAU - Briganti, Alberto AU - Briganti A AD - Department of Urology, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy. FAU - Kimura, Takahiro AU - Kimura T AD - School of Medicine, Department of Urology, Jikei University, Tokyo, Japan. FAU - Egawa, Shin AU - Egawa S AD - School of Medicine, Department of Urology, Jikei University, Tokyo, Japan. FAU - Papalia, Rocco AU - Papalia R AD - Department of Urology, Campus Bio-Medico University, Rome, Italy. FAU - Carrion, Diego M AU - Carrion DM AD - Department of Urology, La Paz University Hospital, Madrid, Spain. AD - European Society of Residents in Urology (ESRU), Arnhem, the Netherlands. FAU - Fiori, Cristian AU - Fiori C AD - School of Medicine, Division of Urology, Department of Oncology, San Luigi Hospital, University of Turin, Orbassano, Turin, Italy. FAU - Shariat, Shahrokh F AU - Shariat SF AD - Department of Urology, Medical University of Vienna, Vienna, Austria. AD - Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. AD - Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan. AD - Department of Urology, Weill Cornell Medical College, New York, NY, USA. AD - Department of Urology, University of Texas Southwestern, Dallas, TX, USA. AD - Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. AD - Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. FAU - Esperto, Francesco AU - Esperto F AD - Department of Urology, Campus Bio-Medico University, Rome, Italy. AD - European Society of Residents in Urology (ESRU), Arnhem, the Netherlands. FAU - Pradere, Benjamin AU - Pradere B AD - Department of Urology, Medical University of Vienna, Vienna, Austria. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20210726 PL - Italy TA - Minerva Urol Nephrol JT - Minerva urology and nephrology JID - 101777299 RN - 0 (Androgen Receptor Antagonists) RN - 0 (Antineoplastic Agents) SB - IM CIN - Minerva Urol Nephrol. 2022 Jun;74(3):360-362. PMID: 35607782 MH - *Androgen Receptor Antagonists/adverse effects MH - *Antineoplastic Agents/adverse effects MH - Humans MH - Male MH - *Prostatic Neoplasms, Castration-Resistant/drug therapy/pathology MH - Quality of Life EDAT- 2021/07/27 06:00 MHDA- 2022/05/26 06:00 CRDT- 2021/07/26 07:09 PHST- 2021/07/27 06:00 [pubmed] PHST- 2022/05/26 06:00 [medline] PHST- 2021/07/26 07:09 [entrez] AID - S2724-6051.21.04431-1 [pii] AID - 10.23736/S2724-6051.21.04431-1 [doi] PST - ppublish SO - Minerva Urol Nephrol. 2022 Jun;74(3):292-301. doi: 10.23736/S2724-6051.21.04431-1. Epub 2021 Jul 26.