Reza Sari Motlagh1, Mohammad Abufaraj2, Keiichiro Mori3, Abdulmajeed Aydh4, Pawel Rajwa5, Satoshi Katayama6, Nico C Grossmann7, Ekaterina Laukhtina8, Hadi Mostafai9, Benjamin Pradere10, Fahad Quhal11, Pierre I Karakiewicz12, Dmitry V Enikeev13, Shahrokh F Shariat14. 1. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Department of Special Surgery, Jordan University Hospital, the University of Jordan, Amman, Jordan; The National Center for Diabetes, Endocrinology and Genetics, The University of Jordan, Amman, Jordan. 3. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. 4. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, King Faisal Medical City, Abha, Saudi Arabia. 5. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Medical University of Silesia, Zabrze, Poland. 6. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 7. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Hospital Zurich, Zurich, Switzerland. 8. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. 9. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 10. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 11. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia. 12. Cancer Prognostics and Health outcomes Unit, University of Montreal Health Center, Montreal, Canada. 13. Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. 14. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Special Surgery, Jordan University Hospital, the University of Jordan, Amman, Jordan; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University of Texas Southwestern, Dallas, TX, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. Electronic address: shahrokh.shariat@meduniwien.ac.at.
Abstract
CONTEXT: Degarelix is associated with high rates of injection site reaction. The US Food and Drug Administration approved relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of advanced prostate cancer patients. OBJECTIVE: This systematic review and network meta-analysis aimed to compare the efficacy and safety of relugolix versus degarelix. EVIDENCE ACQUISITION: A systematic search was performed using major web databases for studies published before January 30, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) extension statement for a network meta-analysis. Studies that compared the efficacy (12-mo castration rate with testosterone ≤50 ng/dl) and safety (adverse events [AEs]) of relugolix or degarelix and of the control group (GnRH agonists) were included. We used the Bayesian approach in the network meta-analysis. EVIDENCE SYNTHESIS: Four studies (n = 2059) met our eligibility criteria. The main efficacy analysis was conducted for two different treatments (relugolix and all doses of degarelix vs GnRH agonists); relugolix (risk ratio [RR] 1.09, 95% credible interval [CrI]: 0.95-1.23) and degarelix (RR 0.98, 95% CrI: 0.91-1.06) were not associated with different 12-mo castration rates. In the subgroup analysis, degarelix 480 mg was significantly associated with a lower castration rate (RR 0.46, 95% CrI: 0.07-0.92). In all efficacy ranking analyses, relugolix achieved the best rank. The safety analyses showed that relugolix (RR 0.99, 95% CrI: 0.6-1.6 and RR 0.72, 95% CrI: 0.4-1.3, respectively) and degarelix (RR 1.1, 95% CrI: 0.75-1.35 and RR 1.05, 95% CrI: 0.42-2.6, respectively) were not associated with either all AE or serious AE rates. In the ranking analyses, degarelix achieved the worst rank of all AEs and the best rank of serious AEs. Relugolix (RR 0.44, 95% CrI: 0.16-1.2) and degarelix (RR 0.74, 95% CrI: 0.37-1.52) were not associated with different cardiovascular event (CVE) rates; both were associated with lower CVE rates than GnRH agonists in the ranking analyses. CONCLUSIONS: We found that the efficacy and safety of relugolix are comparable with those of degarelix, albeit with no injection site reaction. Such data should be interpreted with caution until large-scale direct comparison studies with a longer follow-up are available. PATIENT SUMMARY: We found that relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, has comparable efficacy and safety with degarelix, a parenteral GnRH antagonist, for the treatment of advanced prostate cancer patients.
CONTEXT: Degarelix is associated with high rates of injection site reaction. The US Food and Drug Administration approved relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of advanced prostate cancer patients. OBJECTIVE: This systematic review and network meta-analysis aimed to compare the efficacy and safety of relugolix versus degarelix. EVIDENCE ACQUISITION: A systematic search was performed using major web databases for studies published before January 30, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) extension statement for a network meta-analysis. Studies that compared the efficacy (12-mo castration rate with testosterone ≤50 ng/dl) and safety (adverse events [AEs]) of relugolix or degarelix and of the control group (GnRH agonists) were included. We used the Bayesian approach in the network meta-analysis. EVIDENCE SYNTHESIS: Four studies (n = 2059) met our eligibility criteria. The main efficacy analysis was conducted for two different treatments (relugolix and all doses of degarelix vs GnRH agonists); relugolix (risk ratio [RR] 1.09, 95% credible interval [CrI]: 0.95-1.23) and degarelix (RR 0.98, 95% CrI: 0.91-1.06) were not associated with different 12-mo castration rates. In the subgroup analysis, degarelix 480 mg was significantly associated with a lower castration rate (RR 0.46, 95% CrI: 0.07-0.92). In all efficacy ranking analyses, relugolix achieved the best rank. The safety analyses showed that relugolix (RR 0.99, 95% CrI: 0.6-1.6 and RR 0.72, 95% CrI: 0.4-1.3, respectively) and degarelix (RR 1.1, 95% CrI: 0.75-1.35 and RR 1.05, 95% CrI: 0.42-2.6, respectively) were not associated with either all AE or serious AE rates. In the ranking analyses, degarelix achieved the worst rank of all AEs and the best rank of serious AEs. Relugolix (RR 0.44, 95% CrI: 0.16-1.2) and degarelix (RR 0.74, 95% CrI: 0.37-1.52) were not associated with different cardiovascular event (CVE) rates; both were associated with lower CVE rates than GnRH agonists in the ranking analyses. CONCLUSIONS: We found that the efficacy and safety of relugolix are comparable with those of degarelix, albeit with no injection site reaction. Such data should be interpreted with caution until large-scale direct comparison studies with a longer follow-up are available. PATIENT SUMMARY: We found that relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, has comparable efficacy and safety with degarelix, a parenteral GnRH antagonist, for the treatment of advanced prostate cancer patients.
Authors: Abdulmajeed Aydh; Reza Sari Motlagh; Mohammad Abufaraj; Keiichiro Mori; Satoshi Katayama; Nico Grossmann; Pawel Rajwa; Hadi Mostafai; Ekaterina Laukhtina; Benjamin Pradere; Fahad Quhal; Victor M Schuettfort; Alberto Briganti; Pierre I Karakiewicz; Haron Fajkovic; Shahrokh F Shariat Journal: Arab J Urol Date: 2022-03-30