Mohammad Abufaraj1, Takehiro Iwata2, Shoji Kimura3, Anoud Haddad4, Hashim Al-Ani4, Lana Abusubaih4, Marco Moschini5, Alberto Briganti6, Pierre I Karakiewicz7, Shahrokh F Shariat8. 1. 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; Department of Urology, Medical University of Vienna, Vienna, Austria. 2. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 3. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Jikei University School of Medicine, Tokyo, Japan. 4. Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan. 5. Department of Urology, Medical University of Vienna, Vienna, Austria; Klinik für Urologie, Luzerner Kantonsspital, Lucerne, Switzerland. 6. Division of Oncology, Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy. 7. Division of Urology, University of Montreal Hospital Center, Montreal, Canada. 8. Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan; Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. Electronic address: shahrokh.shariat@meduniwien.ac.at.
Abstract
CONTEXT: Androgen deprivation therapy is the mainstay treatment of metastatic prostate cancer, achieved mainly by gonadotropin-releasing hormone (GnRH) agonists or antagonists. OBJECTIVE: To investigate the differential impact of GnRH agonists and antagonists on clinical safety and oncologic outcomes. EVIDENCE ACQUISITION: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A literature search using the electronic databases (MEDLINE, Web of Science, Cochrane Library, and Scopus) included randomized controlled trials comparing the clinical safety and oncologic outcomes of GnRH agonists and antagonists. The endpoints of interest were the following: (1) treatment-related adverse effects (AEs), (2) prostate-specific antigen (PSA) progression, and (3) overall mortality. The relative risk (RR) was used as the summary statistic, and results were reported with 95% confidence intervals (CIs). EVIDENCE SYNTHESIS: Eight clinical trials (20 published studies) comprising 2632 men met our inclusion criteria; of them, 1646 received GnRH antagonist and 986 had GnRH agonist. Treatment-emerging AEs occurred in 73% patients in the GnRH antagonist group and 68% in the GnRH agonist group (RR: 1.10, 95% CI: 1.04-1.15). Serious AEs occurred in 9.8% of the GnRH antagonist and 11% of the GnRH agonist group (RR: 0.92, 95% CI: 0.73-1.17). Antagonists were associated with higher injection site reaction rates (38%) than agonists (4.8%). GnRH antagonist was associated with fewer cardiovascular events (RR: 0.52, 95% CI: 0.34-0.80). There was no significant difference in PSA progression, but GnRH antagonist was associated with lower overall mortality rates than GnRH agonists (RR: 0.48, 95% CI: 0.26-0.90, p = 0.02). CONCLUSIONS: Existing data indicate that GnRH antagonist use is associated with significantly lower overall mortality and cardiovascular events as compared with agonists. These findings should be interpreted with caution owing to the short follow-up duration and assessment of cardiovascular events as secondary endpoints in the included trials. Further studies are needed to validate or refute these observations. Injection site reactions were significantly higher in the GnRH antagonist group. PATIENT SUMMARY: Gonadotropin-releasing hormone (GnRH) antagonist is associated with lower death rates and cardiovascular events than GnRH agonists, based on the data from trials with short follow-up duration. GnRH agonists are associated with lower adverse events, such as decreased libido, hot flushes, erectile dysfunction, back pain, weight gain, constipation, and injection site reactions. There were no significant differences in prostate-specific antigen progression or fatigue.
CONTEXT: Androgen deprivation therapy is the mainstay treatment of metastatic prostate cancer, achieved mainly by gonadotropin-releasing hormone (GnRH) agonists or antagonists. OBJECTIVE: To investigate the differential impact of GnRH agonists and antagonists on clinical safety and oncologic outcomes. EVIDENCE ACQUISITION: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A literature search using the electronic databases (MEDLINE, Web of Science, Cochrane Library, and Scopus) included randomized controlled trials comparing the clinical safety and oncologic outcomes of GnRH agonists and antagonists. The endpoints of interest were the following: (1) treatment-related adverse effects (AEs), (2) prostate-specific antigen (PSA) progression, and (3) overall mortality. The relative risk (RR) was used as the summary statistic, and results were reported with 95% confidence intervals (CIs). EVIDENCE SYNTHESIS: Eight clinical trials (20 published studies) comprising 2632 men met our inclusion criteria; of them, 1646 received GnRH antagonist and 986 had GnRH agonist. Treatment-emerging AEs occurred in 73% patients in the GnRH antagonist group and 68% in the GnRH agonist group (RR: 1.10, 95% CI: 1.04-1.15). Serious AEs occurred in 9.8% of the GnRH antagonist and 11% of the GnRH agonist group (RR: 0.92, 95% CI: 0.73-1.17). Antagonists were associated with higher injection site reaction rates (38%) than agonists (4.8%). GnRH antagonist was associated with fewer cardiovascular events (RR: 0.52, 95% CI: 0.34-0.80). There was no significant difference in PSA progression, but GnRH antagonist was associated with lower overall mortality rates than GnRH agonists (RR: 0.48, 95% CI: 0.26-0.90, p = 0.02). CONCLUSIONS: Existing data indicate that GnRH antagonist use is associated with significantly lower overall mortality and cardiovascular events as compared with agonists. These findings should be interpreted with caution owing to the short follow-up duration and assessment of cardiovascular events as secondary endpoints in the included trials. Further studies are needed to validate or refute these observations. Injection site reactions were significantly higher in the GnRH antagonist group. PATIENT SUMMARY:Gonadotropin-releasing hormone (GnRH) antagonist is associated with lower death rates and cardiovascular events than GnRH agonists, based on the data from trials with short follow-up duration. GnRH agonists are associated with lower adverse events, such as decreased libido, hot flushes, erectile dysfunction, back pain, weight gain, constipation, and injection site reactions. There were no significant differences in prostate-specific antigen progression or fatigue.
Authors: Azariyas A Challa; Adam Christopher Calaway; Jennifer Cullen; Jorge Garcia; Nihar Desai; Neal L Weintraub; Anita Deswal; Shelby Kutty; Ajay Vallakati; Daniel Addison; Ragavendra Baliga; Courtney M Campbell; Avirup Guha Journal: Curr Treat Options Oncol Date: 2021-04-17
Authors: Alessandro Sciarra; Gian Maria Busetto; Stefano Salciccia; Francesco Del Giudice; Martina Maggi; Felice Crocetto; Matteo Ferro; Ettore De Berardinis; Roberto Mario Scarpa; Francesco Porpiglia; Luca Carmignani; Rocco Damiano; Walter Artibani; Giuseppe Carrieri Journal: Front Endocrinol (Lausanne) Date: 2021-06-14 Impact factor: 5.555