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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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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Microbiota composition is associated with response to ICB in cancer patients, and antibiotic use near treatment start can alter therapy efficacy.
“Recent studies have demonstrated associations between microbiota composition and response to ICB in cancer patients, and evidence suggests that use of antibiotics near the start of treatment can alter therapy efficacy (Chalabi et al., 2020; Chaput et al., 2017; Frankel et al., 2017; Gopalakrishnan et al., 2018; Khan et al., 2021; Matson et al., 2018; Pinato et al., 2019; Routy et al., 2018).”
From Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment (2021) · cites this paper as Chalabi et al., 2020
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Influence of Microbiota on Tumor Immunotherapy
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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
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 31
- Issue
- 4
- Pages
- 525-531
- ISSN
- 0923-7534 (ISSN-L)
- 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 · 2019: 1
- FWCI
- 16.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- 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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