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Minerva Urology and Nephrology 2021 Jul 26

DOI: 10.23736/S2724-6051.21.04431-1

Copyright © 2021 EDIZIONI MINERVA MEDICA

language: English

Androgen receptor axis-targeted agents for non-metastatic castration-resistant prostate cancer impact on overall survival and safety profile: an updated systematic review and meta-analysis

Keiichiro MORI 1, 2 , Fahad QUHAL 1, 3, Satoshi KATAYAMA 1, 4, Hadi MOSTAFAEI 1, 5, Ekaterina LAUKHTINA 1, 6, Victor M. SCHUETTFORT 1, 7, Reza SARI MOTLAGH 1, 8, Nico C. GROSSMANN 1, 9, Pawel RAJWA 1, 10, Guillaume PLOUSSARD 11, Alberto BRIGANTI 12, Takahiro KIMURA 2, Shin EGAWA 2, Rocco PAPALIA 13, Diego M. CARRION 14, 15, Cristian FIORI 16, Shahrokh F. SHARIAT 1, 6, 17, 18, 19, 20, 21, Francesco ESPERTO 13, 15, Benjamin PRADERE 1

1 Department of Urology, Medical University of Vienna, Vienna, Austria; 2 Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; 3 Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia; 4 Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; 5 Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; 6 Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; 7 Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 8 Men’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 9 Department of Urology, University Hospital Zurich, Zurich, Switzerland; 10 Department of Urology, Medical University of Silesia, Zabrze, Poland; 11 Department of Urology, La Croix du Sud Hospital, Quint Fonsegrives, France; 12 Department of Urology, Vita Salute San Raffaele University, Milan, Italy; 13 Department of Urology, Campus Biomedico University of Rome, Rome, Italy; 14 Department of Urology, La Paz University Hospital, Madrid, Spain; 15 European Society of Residents in Urology (ESRU), Arnhem, the Netherlands; 16 Division of Urology, Department of Oncology, San Luigi Hospital, School of Medicine, University of Turin, Orbassano, Turin, Italy; 17 Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan; 18 Department of Urology, Weill Cornell Medical College, New York, NY, USA; 19 Department of Urology, University of Texas Southwestern, Dallas, TX, USA; 20 Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; 21 Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic


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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=4,117) 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.


KEY WORDS: Non-metastatic castration-resistant prostate cancer; Network meta-analysis; Apalutamide; Darolutamide; Enzalutamide

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