Impact of concomitant medications on the oncologic efficacy of systemic therapy in patients with advanced or metastatic urothelial carcinoma: a systematic review and meta-analysis

Impact of concomitant medications on the oncologic efficacy of systemic therapy in patients with advanced or metastatic urothelial carcinoma: a systematic review and meta-analysis

Abstract Background Immune checkpoint inhibitors (ICI) and chemotherapy, including antibody-drug conjugates, are widely used for the treatment of patients with advanced unresectable or metastatic urothelial carcinoma (UC). The majority of elderly patients receive concomitant medications to address v...

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Main Authors: Ichiro Tsuboi, Akihiro Matsukawa, Mehdi Kardoust Parizi, Marcin Miszczyk, Tamás Fazekas, Robert J Schulz, Ekaterina Laukhtina, Tatsushi Kawada, Satoshi Katayama, Takehiro Iwata, Kensuke Bekku, Pawel Rajwa, Koichiro Wada, Katharina Oberneder, Piotr Chlosta, Pierre I. Karakiewicz, Motoo Araki, Shahrokh F. Shariat
Format: Article
Language:English
Published: BMC 2025-04-01
Series:BMC Urology
Subjects:
Concomitant medications
Proton pump inhibitors
Antibiotics, steroids
Opioids
Histamine type-2 receptor antagonists
Immune checkpoint inhibitors
Online Access:https://doi.org/10.1186/s12894-025-01754-2
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Summary:Abstract Background Immune checkpoint inhibitors (ICI) and chemotherapy, including antibody-drug conjugates, are widely used for the treatment of patients with advanced unresectable or metastatic urothelial carcinoma (UC). The majority of elderly patients receive concomitant medications to address various comorbidities. We aimed to evaluate the impact of concomitant medications on oncological outcomes in patients with advanced unresectable or metastatic UC treated with systemic therapy. Material & methods In August 2024, three datasets were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic UC. The review protocol was registered in PROSPERO (CRD42024547335). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis depending on the heterogeneity. Results We identified 16 eligible studies (3 prospective and 13 retrospective) comprising 4,816 patients. Most reported concomitant medications included proton pump inhibitors (PPIs), antibiotics, steroids, and opioids. The use of concomitant PPIs, antibiotics, steroids or opioids during ICI therapy was associated with worsened OS (PPIs: HR: 1.43, 95% CI: 1.31–1.57, p < 0.001; antibiotics: HR: 1.2, 95% CI: 1.04–1.38, p = 0.01; steroids: HR: 1.45, 95% CI: 1.25–1.67, p < 0.001; and opioids: HR: 1.74, 95% CI: 1.46–2.07, p < 0.001). Concomitant use of antibiotics during chemotherapy did not impact OS (HR: 1.01, 95% CI: 0.67–1.51). Conclusions When treating advanced unresectable or metastatic UC with ICI therapy, we need to pay attention to concomitant medications, such as PPIs and antibiotics to avoid reducing the efficacy of ICI therapy. The mechanism of action of these drugs on ICI efficacy requires further examination.
ISSN:1471-2490

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