Impact of Antibiotic Therapy and Metabolic Parameters in Non-Small Cell Lung Cancer Patients Receiving Checkpoint Inhibitors
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Introduction: In the current study, we aimed to assess the impact of antibiotics (ATB) and metabolic parameters on clinical outcome of non-small cell lung carcinoma (NSCLC) patients treated with immune checkpoint inhibitors (ICI). Methods: Data from fifty NSCLC patients referred for ICI between December 2015 and May 2019 were analyzed. All patients underwent 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT) and contrast-enhanced CT at baseline and for response assessment after 6–8 weeks. Patients who received ATB within 1 month before or after the first dose of ICI were compared with those who did not. Response assessment according to iRECIST and EORTC was evaluated, as well as progression-free survival (PFS) and overall survival (OS). For semi-quantitative parameters, we computed metabolic tumor volume (MTV), total lesion glycolysis (TLG) and their variations (∆). Results: Twenty NSCLC cases of 50 (40%) had received ATB. Patients receiving ATB had a higher number of metastases (p = 0.046), and were associated with an elevated tumor burden, expressed by TLG (687 vs. 235.3, p = 0.007) and MTV (125.6 vs. 40.6, p = 0.002), compared to no-ATB patients. According to iRECIST, progressive disease rate was significantly higher for ATB group (64.7% vs. 27.6%, p = 0.029). Likewise, PFS was shorter for ATB compared to no-ATB (median 4.1 vs. 12.4 months, p = 0.004), while no difference for OS was detected. On multivariate analysis, the effect of ATB remained significant for poor PFS along with performance status (ECOG ≥ 1), and ∆SUVmax. Conclusions: ATB therapy seems to be associated with a worse treatment response, PFS, and higher metabolic tumor burden in NSCLC patients treated with ICI.
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Administration of high-risk antibiotics likely constitutes a surrogate for poor disease status and increased systemic inflammation before CAR-T, rather than causally driving altered CAR-T responsiveness.
“However, our results suggest that administration of these classes of antibiotics constitutes a likely surrogate for poor disease status and a state of increased systemic inflammation prior to initiation of CAR-T cell therapy, as was recently suggested in cancer patients treated with other ICBs28,35.”
From A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy (2023) · cites this paper as [35]
Administration of these antibiotics likely serves as a surrogate for poor disease status and increased systemic inflammation before CAR-T initiation.
“However, our results suggest that administration of these classes of antibiotics constitutes a likely surrogate for poor disease status and a state of increased systemic inflammation prior to initiation of CAR-T cell therapy, as was recently suggested in cancer patients treated with other ICBs28,35.”
From A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy (2023) · cites this paper as [35]
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- Authors
- Castello, A., Rossi, S., Toschi, L., & Lopci, E.
- Affiliations
- IRCCS Humanitas Research Hospital (IT)
- Corresponding author
- Lopci, Egesta
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2021-03-17
- Volume
- 10
- Issue
- 6
- Pages
- 1251
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC8002619
- OpenAlex
- W3138943871
- Cited by
- 36
- References
- 37
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 6 · 2023: 10 · 2022: 10 · 2021: 2
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Associazione Italiana per la Ricerca sul Cancro (18923)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- non-small cell lung cancer, immune checkpoint inhibitors, antibiotic therapy, metabolic tumor volume, total lesion glycolysis, FDG PET/CT, progression-free survival, treatment response, immune-related adverse events
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