Cited by 294Cancer Immunotherapy and BiomarkersLung Cancer Treatments and MutationsLung Cancer Diagnosis and Treatment

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Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: pooled post hoc analyses of the OAK and POPLAR trials

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Chalabi, M., Cardona, A., Nagarkar, D.R., Dhawahir Scala, A., Gandara, D.R., Rittmeyer, A., Albert, M.L., Powles, T., Kok, M., Herrera, F.G.·2020·Annals of Oncology

DOI 10.1016/j.annonc.2020.01.006

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Abstract

BACKGROUND: Preclinical data have shown that proton pump inhibitors (PPI) can modulate the microbiome, and single-arm studies suggested that antibiotics (ATB) may decrease the efficacy of immune checkpoint inhibitors (ICI), but randomized controlled trial data are lacking. This pooled analysis evaluated the effect of ATB and PPI on outcome in patients randomized between ICI and chemotherapy. PATIENTS AND METHODS: This retrospective analysis used pooled data from the phase II POPLAR (NCT01903993) and phase III OAK (NCT02008227) trials, which included 1512 patients with previously treated non-small-cell lung cancer (NSCLC) randomly assigned to receive atezolizumab (n = 757) or docetaxel (n = 755). The main objective of this analysis was to assess the impact of ATB and PPI use on overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 169 (22.3%) patients in the atezolizumab group and 202 (26.8%) in the docetaxel group received ATB, and 234 (30.9%) and 260 (34.4%), respectively, received PPI. Multivariate analysis in all patients revealed that ATB were associated with shorter OS [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.04-1.39], as was PPI (HR 1.26, 95% CI 1.10-1.44). Within the atezolizumab population, OS was significantly shorter in patients who received ATB (8.5 versus 14.1 months, HR 1.32, 95% CI 1.06-1.63, P = 0.01) or PPI (9.6 versus 14.5 months, HR 1.45, 95% CI 1.20-1.75, P = 0.0001). PPI use was associated with shorter PFS in the atezolizumab population (1.9 versus 2.8 months, HR 1.30, 95% CI 1.10-1.53, P = 0.001). There was no association between ATB and PPI use and PFS or OS within the docetaxel population. CONCLUSION: In this unplanned analysis from two randomized trials, data suggest that ATB or PPI use in patients with metastatic NSCLC is associated with poor outcome and may influence the efficacy of ICI.

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Authors: Chalabi, M., Cardona, A., Nagarkar, D. R., Dhawahir Scala, A., Gandara, D. R., Rittmeyer, A., Albert, M. L., Powles, T., Kok, M., & Herrera, F. G.
Affiliations: The Netherlands Cancer Institute (NL)
F. Hoffmann-La Roche AG (CH)
Genentech (US)
UC Davis Comprehensive Cancer Center (US)
Barts Cancer Institute (GB)
Centre Hospitalier Universitaire Vaudois (CH)
Corresponding author: Chalabi, M.
Herrera, F.G.
ORCID: Chalabi, M.
Cardona, A.
Nagarkar, D.R.
Gandara, D.R.
Rittmeyer, A.
Albert, M.L.
Powles, T.
Kok, M.
Herrera, F.G.
Venue: Annals of Oncology
Publisher: Elsevier BV
Published: 2020-04
Volume: 31
Issue: 4
Pages: 525-531
ISSN: 0923-7534 (ISSN-L)
DOI: 10.1016/j.annonc.2020.01.006
OpenAlex: W3000696551
Semantic Scholar: 1d776be113ebef731e6a54113731c7db0cd5ccf0
Cited by: 294
References: 24
Citations by year: 2026: 22 · 2025: 40 · 2024: 42 · 2023: 44 · 2022: 60 · 2021: 55 · 2020: 29
FWCI: 16.98
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Annals of Oncology (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
IRIS (submittedVersion, cc-by-nc-nd)
SERVAL (Université de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders: F. Hoffmann-La Roche Ltd
F Hoffmann-La Roche
Genentech
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords: non-small cell lung cancer, atezolizumab, proton pump inhibitors, antibiotics, immune checkpoint inhibitors, chemotherapy, docetaxel, microbiome, overall survival, progression-free survival, OAK trial, POPLAR trial, drug interactions, immunotherapy efficacy, previously treated patients, PD-L1 expression, PD-1 expression, PD-1/PD-L1 blockade
MeSH terms: Anti-Bacterial Agents, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Retrospective Studies, Proton Pump Inhibitors, Antibodies, Monoclonal, Humanized

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Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: pooled post hoc analyses of the OAK and POPLAR trials

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