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

Clin Genitourin Cancer

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:

Published: December 2024

Immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) are standard treatments for advanced renal cell carcinoma, but the impact of other medications taken alongside these treatments is uncertain.
A review of 22 studies involving over 16,000 patients found that certain concomitant medications like proton pump inhibitors and antibiotics negatively affect overall survival when taken with ICIs, while statins, renin-angiotensin system inhibitors, and beta-blockers improve survival when combined with TKIs.
Clinicians should evaluate patients' baseline medications before starting systemic therapy for metastatic RCC, as some drugs can either reduce or enhance the effectiveness of cancer treatments.

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.

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http://dx.doi.org/10.1016/j.clgc.2024.102237	DOI Listing

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