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]
Citations
Cites
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Cancer immunotherapy using checkpoint blockade
Ribas, A., & Wolchok, J. D. (2018) · Science · doi:10.1126/science.aar4060 · Cited by 6,791
Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors
Routy, B., Le Chatelier, E., Derosa, L., Duong, C. P. M., Alou, M. T., Daillère, R., Fluckiger, A., Messaoudene, M., Rauber, C., Roberti, M. P., et al. (2018) · Science · doi:10.1126/science.aan3706 · Cited by 5,671
Mazières, J., Drilon, A. E. D. C., Lusque, A., Mhanna, L., Cortot, A. B., Mezquita, L., Thai, A. A., Mascaux, C., Couraud, S., Veillon, R., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz167 · Cited by 1,377
Proton pump inhibitors affect the gut microbiome
Imhann, F., Bonder, M. J., Vich Vila, A., Fu, J., Mujagic, Z., Vork, L., Tigchelaar, E. F., Jankipersadsing, S. A., Cenit, M. C., Harmsen, H. J. M., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-310376 · Cited by 1,371 · cited 1×
“17 22 However, a high percentage of the available evidence has limitations in its methodology and design, with some controversy over the inclusion criteria used, small sample sizes, and a lack of consideration of potential confounding factors.”
BackgroundWolchok, J. D., Chiarion-Sileni, V., Gonzalez, R., Grob, J., Rutkowski, P., Lao, C. D., Cowey, C. L., Schadendorf, D., Wagstaff, J., Dummer, R., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.21.02229 · Cited by 1,160
Gettinger, S. N., Horn, L., Jackman, D. M., Spigel, D. R., Antonia, S. J., Hellmann, M. D., Powderly, J. D., Heist, R. S., Sequist, L. V. D., Smith, D. C., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.77.0412 · Cited by 745
25 Years of Proton Pump Inhibitors: A Comprehensive Review
Strand, D. S., Kim, D., & Peura, D. A. (2016) · Gut and Liver · doi:10.5009/gnl15502 · Cited by 676
Paz-Ares, L. G., Vicente, D., Tafreshi, A., Robinson, A. G., Parra, H. J. S., Mazières, J., Hermes, B., Çiçin, İ., Medgyasszay, B., Rodríguez‐Cid, J. R., et al. (2020) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2020.06.015 · Cited by 630
Jackson, M. A., Verdi, S., Maxan, M.-E., Shin, C. M., Zierer, J., Bowyer, R. C. E., Martin, T., Williams, F. M. K., Menni, C., Bell, J. T., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05184-7 · Cited by 616
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Research works printed but not linked: 1
- Universitario, 2022, Evaluación de la interacción de capecitabina con inhibidores de la bomba de protones en pacientes con cáncer de colon metastásico [Evaluation of the interaction of capecitabine with proton pump inhibitors in patients with metastatic colon cancer], Rev OFIL·ILAPHAR, 1
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Gamrath, L., Pedersen, T. B., Møller, M. V., Volmer, L. M., Holst-Christensen, L., Vestermark, L. W., & Donskov, F. (2025) · Current Oncology Reports · doi:10.1007/s11912-024-01622-6 · Cited by 30
“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
Zitvogel, L., Derosa, L., Routy, B., Loibl, S., Heinzerling, L., de Vries, I. J. M., Engstrand, L., ONCOBIOME Network, Silva, C. A. C., Barbieri, D., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03608-8 · Cited by 23
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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