PMID- 38291115
OWN - NLM
STAT- MEDLINE
DCOM- 20240201
LR  - 20240206
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 14
IP  - 1
DP  - 2024 Jan 30
TI  - Proton pump inhibitors and potassium competitive acid blockers decrease 
      pembrolizumab efficacy in patients with metastatic urothelial carcinoma.
PG  - 2520
LID - 10.1038/s41598-024-53158-1 [doi]
LID - 2520
AB  - 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.
CI  - (c) 2024. The Author(s).
FAU - Iida, Keitaro
AU  - Iida K
AD  - Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City 
      University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
AD  - Department of Urology, Gamagori City Hospital, Gamagori City, Japan.
FAU - Naiki, Taku
AU  - Naiki T
AD  - Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City 
      University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. 
      naiki@med.nagoya-cu.ac.jp.
FAU - Etani, Toshiki
AU  - Etani T
AD  - Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City 
      University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
FAU - Nagai, Takashi
AU  - Nagai T
AD  - Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City 
      University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
FAU - Sugiyama, Yosuke
AU  - Sugiyama Y
AD  - Department of Pharmacy, Nagoya City University Hospital, Nagoya, Japan.
FAU - Isobe, Teruki
AU  - Isobe T
AD  - Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City 
      University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
FAU - Aoki, Maria
AU  - Aoki M
AD  - Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City 
      University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
FAU - Nozaki, Satoshi
AU  - Nozaki S
AD  - Department of Urology, Anjo Kosei Hospital, Anjo City, Japan.
FAU - Noda, Yusuke
AU  - Noda Y
AD  - Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City 
      University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
AD  - Department of Urology, Toyota Kosei Hospital, Toyota City, Japan.
FAU - Shimizu, Nobuhiko
AU  - Shimizu N
AD  - Department of Urology, Anjo Kosei Hospital, Anjo City, Japan.
FAU - Tomiyama, Nami
AU  - Tomiyama N
AD  - Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City 
      University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
AD  - Department of Urology, Gamagori City Hospital, Gamagori City, Japan.
FAU - Gonda, Masakazu
AU  - Gonda M
AD  - Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City 
      University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
FAU - Kamiya, Hiroyuki
AU  - Kamiya H
AD  - Department of Urology, Daido Hospital, Nagoya City, Japan.
FAU - Kubota, Hiroki
AU  - Kubota H
AD  - Department of Urology, Kainan Hospital, Yatomi City, Japan.
FAU - Nakane, Akihiro
AU  - Nakane A
AD  - Department of Urology, Gamagori City Hospital, Gamagori City, Japan.
AD  - Department of Education and Research Center for Community Medicine, Nagoya City 
      University Graduate School of Medical Sciences, Nagoya, Japan.
FAU - Ando, Ryosuke
AU  - Ando R
AD  - Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City 
      University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
FAU - Kawai, Noriyasu
AU  - Kawai N
AD  - Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City 
      University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
FAU - Yasui, Takahiro
AU  - Yasui T
AD  - Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City 
      University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
LA  - eng
PT  - Journal Article
DEP - 20240130
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Proton Pump Inhibitors)
RN  - DPT0O3T46P (pembrolizumab)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Steroids)
RN  - 9100L32L2N (Metformin)
RN  - 0 (Antibodies, Monoclonal, Humanized)
SB  - IM
MH  - Humans
MH  - Proton Pump Inhibitors/pharmacology/therapeutic use
MH  - *Carcinoma, Transitional Cell/drug therapy
MH  - Retrospective Studies
MH  - *Urinary Bladder Neoplasms/pathology
MH  - Anti-Bacterial Agents/therapeutic use
MH  - Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
MH  - Steroids/therapeutic use
MH  - *Metformin/therapeutic use
MH  - *Antibodies, Monoclonal, Humanized
PMC - PMC10827730
COIS- The authors declare no competing interests.
EDAT- 2024/01/31 00:42
MHDA- 2024/02/01 06:42
PMCR- 2024/01/30
CRDT- 2024/01/30 23:22
PHST- 2022/10/12 00:00 [received]
PHST- 2024/01/29 00:00 [accepted]
PHST- 2024/02/01 06:42 [medline]
PHST- 2024/01/31 00:42 [pubmed]
PHST- 2024/01/30 23:22 [entrez]
PHST- 2024/01/30 00:00 [pmc-release]
AID - 10.1038/s41598-024-53158-1 [pii]
AID - 53158 [pii]
AID - 10.1038/s41598-024-53158-1 [doi]
PST - epublish
SO  - Sci Rep. 2024 Jan 30;14(1):2520. doi: 10.1038/s41598-024-53158-1.