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Proton pump inhibitors/potassium-competitive acid blockers decrease pembrolizumab efficacy in patients with metastatic urothelial carcinoma

Authors :
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
Takahiro Yasui
Publication Year :
2022
Publisher :
Research Square Platform LLC, 2022.

Abstract

Background We elucidated the efficacy of gut microbiome–altering drugs on pembrolizumab efficacy in patients with metastatic urothelial carcinoma (mUC). Methods Clinical data were analyzed retrospectively from 135 mUC patients 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). Results 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. Multivariate analysis excluded opioid and steroid use due to a significant correlation with previously reported predictive factors for disease progression or death. Multivariate analysis highlighted only PPI/P-CAB use as an independent prognostic factor for disease progression (hazards ratio: 1.63, 95% confidence interval: 1.08–2.45, p = 0.021) but not death (p = 0.123). Propensity score matching, including opioid and steroid use, revealed PPI/P-CAB users showed shorter PFS than non-PPI/P-CAB users (p = 0.006). Conclusions PPI/P-CAB may decrease the efficacy of pembrolizumab therapy for mUC, possibly via gut microbiome modulation.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........4c7b93b89004351549e250c833b58e10
Full Text :
https://doi.org/10.21203/rs.3.rs-2158631/v1