1. Proton pump inhibitors and potassium competitive acid blockers decrease pembrolizumab efficacy in patients with metastatic urothelial carcinoma
- Author
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Keitaro Iida, Taku Naiki, Toshiki Etani, Takashi Nagai, Yosuke Sugiyama, Teruki Isobe, Maria Aoki, Satoshi Nozaki, Yusuke Noda, Nobuhiko Shimizu, Nami Tomiyama, Masakazu Gonda, Hiroyuki Kamiya, Hiroki Kubota, Akihiro Nakane, Ryosuke Ando, Noriyasu Kawai, and Takahiro Yasui
- Subjects
Medicine ,Science - Abstract
Abstract We elucidated the efficacy of gut microbiome–altering drugs on pembrolizumab efficacy in patients with metastatic urothelial carcinoma (mUC). Clinical data were analyzed retrospectively from 133 patients with mUC who received second-line pembrolizumab therapy between January 2018 and January 2021, following failed platinum-based chemotherapy. We evaluated the effects of gut microbiome–altering drugs (proton pump inhibitors [PPI]/potassium-competitive acid blockers [P-CAB], H2 blockers, antibiotics, non-steroidal anti-inflammatory drugs [NSAIDs], metformin, antipsychotics, steroids, and opioids), taken by patients within 30 days before/after pembrolizumab treatment, on progression-free survival (PFS) and overall survival (OS). Fifty-one patients received PPI/P-CAB (37/14, respectively); H2 blockers, 7; antibiotics, 35; NSAIDs, 22; antipsychotics, 8; metformin, 3; steroids, 11; and opioids, 29. Kaplan–Meier curves revealed PPI or P-CAB users showed shorter PFS than non-PPI-P-CAB users (p = 0.001, p = 0.005, respectively). Multivariate analysis highlighted PPI/P-CAB use as the only independent prognostic factor for disease progression (hazards ratio: 1.71, 95% confidence interval: 1.14–2.07, p = 0.010) but not death (p = 0.177). Proton pump inhibitors/potassium-competitive acid blockers may decrease the efficacy of pembrolizumab therapy for mUC, possibly via gut microbiome modulation.
- Published
- 2024
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