You have accessJournal of UrologyBladder Cancer: Invasive II (MP41)1 Sep 2021MP41-15 PROTON PUMP INHIBITOR USE IS A NEGATIVE PROGNOSTIC FACTOR FOR METASTATIC UROTHELIAL CARCINOMA PROGRESSION IN PEMBROLIZUMAB-TREATED PATIENTS Keitaro Iida, Takashi Nagai, Satoshi Nozaki, Toshiki Etani, Taku Naiki, Akihiro Nakane, Hidetoshi Akita, Hiroki Kubota, Hiroyuki Kamiya, Noriyasu Kawai, and Takahiro Yasui Keitaro IidaKeitaro Iida More articles by this author , Takashi NagaiTakashi Nagai More articles by this author , Satoshi NozakiSatoshi Nozaki More articles by this author , Toshiki EtaniToshiki Etani More articles by this author , Taku NaikiTaku Naiki More articles by this author , Akihiro NakaneAkihiro Nakane More articles by this author , Hidetoshi AkitaHidetoshi Akita More articles by this author , Hiroki KubotaHiroki Kubota More articles by this author , Hiroyuki KamiyaHiroyuki Kamiya More articles by this author , Noriyasu KawaiNoriyasu Kawai More articles by this author , and Takahiro YasuiTakahiro Yasui More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002062.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recently, the role of the gut microbiome in inflammatory disease and carcinogenesis has become apparent. Specifically, higher gut microbiome diversity is associated with improved responses to anti-PD-1 immunotherapy, suggesting that the gut microbiome impacts immuno-oncology in a systemic manner. The present study elucidated the impact of drugs known to alter gut microbiome balance on pembrolizumab (PEM) efficacy in metastatic urothelial carcinoma (mUC) patients. METHODS: Clinicopathologic data of 115 mUC patients receiving second-line PEM (following failed platinum-based chemotherapy) between January 2018 and January 2021 were retrospectively analyzed. Study protocols were approved by the Nagoya City University research ethics committee (No. 60-18-0060). Impact of gut microbiome-altering medications (proton pump inhibitors (PPI), antibiotics (ATB), metformin, and antipsychotics) taken during — or within 30 days on either side of — the PEM treatment period on progression-free survival (PFS), time-to-treatment failure (TTF), and adverse events was statistically evaluated. Kaplan-Meier survival curves were constructed and survival rates were compared using the log-rank test. Uni- and multivariate analyses were performed using the Cox proportional hazard regression model. RESULTS: Patient mean age was 73 years. Primary affected sites were bladder (48.7 %), upper urinary tract (46.1 %), and a combination of the two (5.2 %). Eastern Cooperative Oncology Group performance status at PEM initiation was 0, 41, 1, 55, 2, and 19. No drug of interest was associated with adverse gastrointestinal events (diarrhea and constipation). Univariate analysis demonstrated that PPI use predicted a significantly shorter PFS interval (p <0.0001), and that PPI or ATB use predicted a significantly shorter TTF interval (p <0.01 and p <0.05, respectively). Multivariate analysis demonstrated that PPI use was an independent prognostic factor for both cancer progression and treatment failure. CONCLUSIONS: Possibly via gut microbiome modulation, PPI use may decrease efficacy of PEM in the treatment of mUC. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e766-e767 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Keitaro Iida More articles by this author Takashi Nagai More articles by this author Satoshi Nozaki More articles by this author Toshiki Etani More articles by this author Taku Naiki More articles by this author Akihiro Nakane More articles by this author Hidetoshi Akita More articles by this author Hiroki Kubota More articles by this author Hiroyuki Kamiya More articles by this author Noriyasu Kawai More articles by this author Takahiro Yasui More articles by this author Expand All Advertisement PDF downloadLoading ...