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The Impact of Concomitant Medications on the Overall Survival of Patients Treated With Systemic Therapy for Advanced or Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis Publisher Pubmed



Tsuboi I1, 2, 3 ; Matsukawa A1, 4 ; Kardoust Parizi M1, 5 ; Miszczyk M1, 6 ; Fazekas T1, 7 ; Schulz RJ1, 8 ; Mancon S1, 9 ; Litterio G10 ; Laukhtina E1, 11 ; Kawada T1, 3 ; Katayama S1, 3 ; Iwata T1, 3 ; Bekku K1, 3 ; Rajwa P1, 12 Show All Authors
Authors
  1. Tsuboi I1, 2, 3
  2. Matsukawa A1, 4
  3. Kardoust Parizi M1, 5
  4. Miszczyk M1, 6
  5. Fazekas T1, 7
  6. Schulz RJ1, 8
  7. Mancon S1, 9
  8. Litterio G10
  9. Laukhtina E1, 11
  10. Kawada T1, 3
  11. Katayama S1, 3
  12. Iwata T1, 3
  13. Bekku K1, 3
  14. Rajwa P1, 12
  15. Wada K1, 2
  16. Karakiewicz PI13
  17. Araki M3
  18. Shariat SF1, 7, 11, 14, 15, 16, 17, 18, 19
Show Affiliations
Authors Affiliations
  1. 1. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  2. 2. Department of Urology, Shimane University Faculty of Medicine, Shimane, Japan
  3. 3. Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  4. 4. Department of Urology, Jikei University School of Medicine, Tokyo, Japan
  5. 5. Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Collegium Medicum - Faculty of Medicine, WSB University, Dabrowa Gornicza, Poland
  7. 7. Department of Urology, Semmelweis University, Budapest, Hungary
  8. 8. Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  9. 9. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
  10. 10. Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, Urology Unit, Chieti, Italy
  11. 11. Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russian Federation
  12. 12. Second Department of Urology, Centre of Postgraduate Medical Education, Warsaw, Poland
  13. 13. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, QC, Canada
  14. 14. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, United States
  15. 15. Department of Urology, Weill Cornell Medical College, New York, NY, United States
  16. 16. Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
  17. 17. Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan
  18. 18. Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria
  19. 19. Research Center for Evidence Medicine, Urology Department Tabriz University of Medical Sciences, Tabriz, Iran

Source: Clinical Genitourinary Cancer Published:2024


Abstract

Although immune checkpoint inhibitors (ICI) and/or tyrosine kinase inhibitors (TKI) are the standard treatment of advanced unresectable or metastatic renal cell carcinoma (RCC), the impact of concomitant medications remains unclear. We aimed to evaluate the impact of concomitant medications on survival outcomes in patients treated with systemic therapy for advanced unresectable or metastatic RCC. In August 2024, PubMed, Scopus, and Web of Science were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic RCC (PROSPERO: CRD42024573252). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis according to heterogeneity. We identified 22 eligible studies (5 prospective and 17 retrospective) comprising 16,072 patients. Concomitant medications included proton pump inhibitors (PPI) (n = 3959), antibiotics (n = 571), statins (n = 5466), renin-angiotensin system inhibitors (RASi) (n = 6615), and beta-blockers (n = 1964). Both concomitant PPI and antibiotics were significantly associated with worse OS in patients treated with ICI (PPI: HR: 1.22, P = .01, and antibiotics: HR: 2.09, P < .001). Concomitant statins, RASi, or beta-blocker were significantly associated with improved OS in patients treated with TKI (statins: HR: 0.81, P = .03, RASi: HR: 0.63, P < .001, beta-blocker: HR: 0.69, P < .001, respectively). In patients treated with ICI, RASi was significantly associated with improved OS (HR: 0.64, P = .02). Concomitant use of antibiotics or PPI with ICI can reduce its oncologic efficacy. Conversely, concomitant statins, RASi, or beta-blockers can enhance the oncologic efficacy of TKI. When initiating systemic therapy for metastatic RCC, it may be important for clinicians to assess baseline co-medications and recognize their possible positive or negative effects. © 2024 The Authors
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