TY - JOUR
T1 - The Impact of Concomitant Medications on the Overall Survival of Patients Treated with Systemic Therapy for Advanced or Metastatic Renal Cell Carcinoma
T2 - A Systematic Review and Meta-analysis
AU - Tsuboi, Ichiro
AU - Matsukawa, Akihiro
AU - Kardoust Parizi, Mehdi
AU - Miszczyk, Marcin
AU - Fazekas, Tamás
AU - Schulz, Robert J.
AU - Mancon, Stefano
AU - Litterio, Giulio
AU - Laukhtina, Ekaterina
AU - Kawada, Tatsushi
AU - Katayama, Satoshi
AU - Iwata, Takehiro
AU - Bekku, Kensuke
AU - Rajwa, Pawel
AU - Wada, Koichiro
AU - Karakiewicz, Pierre I.
AU - Araki, Motoo
AU - Shariat, Shahrokh F.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
KW - Chemotherapy
KW - Concomitant medications metastatic renal cell carcinoma
KW - Immune checkpoint inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85208934410&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85208934410&partnerID=8YFLogxK
U2 - 10.1016/j.clgc.2024.102237
DO - 10.1016/j.clgc.2024.102237
M3 - Review article
C2 - 39546952
AN - SCOPUS:85208934410
SN - 1558-7673
VL - 22
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 6
M1 - 102237
ER -