The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Effect of Concomitant Use of Proton Pump Inhibitors on Immunotherapy Clinical Response in Advanced Cancer Patients: Real-Life Setting
Abstract
The alteration of the gut microbiota mediated by proton pump inhibitor (PPI) drugs could be involved in the clinical response associated with immunotherapy [immunocheckpoint inhibitors (ICIs)] in cancer patients. Due to the current controversy in the scientific evidence, it has been proposed to evaluate the correlation between the concomitant use of PPIs and the effectiveness of immunotherapy in a real clinical practice setting. Single-center retrospective cohort study that included patients treated with anti-PD-1 or anti-CTLA4, including nivolumab, pembrolizumab, atezolizumab, or the combination ipilimumab-nivolumab in metastatic neoplastic disease. The clinical effectiveness of ICI, measured in progression-free survival (PFS) and overall survival (OS), was compared between the PPI-use versus PPI-no-use group. PPI-use group was associated with lower PFS [hazard ratio (HR):1.89 (1.38-2.59), P<0.001] and OS [HR: 2.02 (1.45-2.82), P<0.001] versus PPI-no-use group. However, this difference was not observed for pembrolizumab PFS [HR: 1.38 (0.93-2.39), P=0.160] and OS [HR: 1.41 (0.81-2.44), P=0.187]. The study showed significantly lower PFS and OS in the chronic PPI-use group (P<0.001), recent PPI-use group (P<0.001) and concomitant PPI-use group (P=0.001, 0.007) versus PPI-no-use group. However, late PPI use >30 days after the onset of ICI has no significant effect on the efficacy of treatment [HR: 0.92 (0.49-1.70), P=0.791; HR: 1.10 (0.59-2.05), P=0.756]. The concomitant use of PPIs in immunotherapy is associated with worse clinical outcomes compared with the group without PPI use. In addition, the study shows how the late use of PPIs does not have a significant effect on clinical benefit.
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“Pending further confirmation in large clinical studies, such guidelines might be extended to recommend healthy diets and to warn against the use of proton pump inhibitors 95 , benzodiazepines 96 and over-the-counter probiotics 97 , which are all associated with poor immunotherapy outcome.”
From Impact of the ONCOBIOME network in cancer microbiome research (2025) · cites this paper as [95]
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Cited by
Sorted by citations
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“The study suggested a treatment window where starting PPIs four weeks after initiating immunotherapy might mitigate their negative effects [63].”
Impact of the ONCOBIOME network in cancer microbiome research
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Metadata
- Authors
- Cantarelli, L., Gutiérrez Nicolás, F., García Gil, S., Morales Barrios, J. A., Oramas Rodriguez, J., & Nazco Casariego, G. J.
- Affiliations
- Servicio de Farmacia, Hospital Nuestra Señora de Guadalupe, La Gomera, Spain
- Servicio de Farmacia, Complejo Hospitalario Universitario de Canarias, Tenerife, Spain
- Servicio de Oncología médica, Complejo Hospitalario Universitario de Canarias, Tenerife, Spain
- Corresponding author
- Cantarelli, Lorenzo
- ORCID
- Cantarelli, Lorenzo
- Venue
- Journal of Immunotherapy
- Published
- 2023-11-06
- Volume
- 47
- Issue
- 1
- Pages
- 21-31
- ISSN
- 1524-9557 (ISSN-L)
- OpenAlex
- W4388493273
- Cited by
- 4
- References
- 30
- Citations by year
- 2026: 1 · 2025: 3
- FWCI
- 0.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Immunotherapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- proton pump inhibitors, immunotherapy, immune checkpoint inhibitors, anti-PD-1, anti-CTLA-4, nivolumab, pembrolizumab, atezolizumab, gut microbiota, progression-free survival, overall survival, advanced cancer, metastatic cancer
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