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

Ichiro Tsuboi; Akihiro Matsukawa; Mehdi Kardoust Parizi; Marcin Miszczyk; Tamás Fazekas; Robert J Schulz; Stefano Mancon; Giulio Litterio; Ekaterina Laukhtina; Tatsushi Kawada; Satoshi Katayama; Takehiro Iwata; Kensuke Bekku; Pawel Rajwa; Koichiro Wada; Pierre I Karakiewicz; Motoo Araki; Shahrokh F Shariat

doi:10.1016/j.clgc.2024.102237

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

Clin Genitourin Cancer. 2024 Oct 17;22(6):102237. doi: 10.1016/j.clgc.2024.102237. Online ahead of print.

Authors

Ichiro Tsuboi¹, Akihiro Matsukawa², Mehdi Kardoust Parizi³, Marcin Miszczyk⁴, Tamás Fazekas⁵, Robert J Schulz⁶, Stefano Mancon⁷, Giulio Litterio⁸, Ekaterina Laukhtina⁹, Tatsushi Kawada¹⁰, Satoshi Katayama¹⁰, Takehiro Iwata¹⁰, Kensuke Bekku¹⁰, Pawel Rajwa¹¹, Koichiro Wada¹², Pierre I Karakiewicz¹³, Motoo Araki¹⁴, Shahrokh F Shariat¹⁵

Affiliations

¹ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Shimane University Faculty of Medicine, Shimane, Japan; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
² Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Jikei University School of Medicine, Tokyo, Japan.
³ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Collegium Medicum - Faculty of Medicine, WSB University, Dąbrowa Górnicza, Poland.
⁵ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Semmelweis University, Budapest, Hungary.
⁶ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁷ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
⁸ Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University, Urology Unit, Chieti, Italy.
⁹ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia.
¹⁰ 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.
¹¹ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Second Department of Urology, Centre of Postgraduate Medical Education, Warsaw, Poland.
¹² Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Shimane University Faculty of Medicine, Shimane, Japan.
¹³ Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Quebec, Canada.
¹⁴ Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
¹⁵ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Semmelweis University, Budapest, Hungary; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czechia; Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Research Center for Evidence Medicine, Urology Department Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: shahrokh.shariat@meduniwien.ac.at.

PMID: 39546952
DOI: 10.1016/j.clgc.2024.102237

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.

Keywords: Chemotherapy; Concomitant medications metastatic renal cell carcinoma; Immune checkpoint inhibitors.

Publication types

Review