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Predictive impact of antibiotics in patients with advanced non small-cell lung cancer receiving immune checkpoint inhibitors

Antibiotics immune checkpoint inhibitors in advanced NSCLC

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Abstract

Purpose

In this study, we test the hypothesis that the use of ATB reduces the efficacy of PD(L)1-targeting mAb.

Methods

We included patients with locally advanced, inoperable or metastatic, EGFR wildtype and ALK-negative non-small-cell lung cancer (NSCLC) who received a PD(L)1 targeting mAb (immune checkpoint inhibitor, ICI) between January 2013 and December 2017. The primary study objective was to assess the predictive impact of ATB use within 2 months prior to starting ICI treatment on overall survival from the time of starting ICI treatment (OS-ICI).

Results

33 out of 218 evaluable patients (15.1%) received ATB within 2 months prior to starting ICI treatment. The use of ATB prior to starting ICI was associated with a lower rate of radiological response (18.2 vs. 28.3%, respectively, P = 0.02). PFS was significantly shorter in patients receiving ATB within 2 months prior to ICI compared to those not receiving ATB (median PFS 1.4 vs. 5.5 months, HR = 2.22, P < 0.01). OS-ICI was significantly shorter in NSCLC patients receiving ATB within 2 months prior to ICI compared to those not receiving ATB (median OS-ICI 1.8 vs. 15.4 months, HR = 2.61, P < 0.01; adjusted HR = 3.73, P < 0.01).

Conclusion

The results of this study suggest that ATB may have a deleterious effect in patients with advanced NSCLC receiving ICI treatment, and more research seems to be justified to explore potential mechanisms.

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Authors and Affiliations

  1. University of Basel, Basel, Switzerland

    Anne Schett & Markus Joerger

  2. Department of Medical Oncology, University Hospital, Basel, Switzerland

    Sacha I. Rothschild

  3. Department of Medical Oncology and Hematology, University Hospital, Zurich, Switzerland

    Alessandra Curioni-Fontecedro

  4. Division of Clinical Pharmacology& Toxicology, University Hospital, Basel, Switzerland

    Stephan Krähenbühl

  5. Department of Medical Oncology, Cantonal Hospital, Rorschacherstr. 95, 9007, St. Gallen, Switzerland

    Martin Früh, S. Schmid, Christoph Driessen & Markus Joerger

  6. University of Bern, Bern, Switzerland

    Martin Früh

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  1. Anne Schett
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Correspondence to Markus Joerger.

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Supplementary material 1 (DOCX 19 kb)

280_2019_3993_MOESM2_ESM.tif

Supplementary material 2 Overall survival from diagnosis of palliative NSCLC in patients receiving antibiotics (ATB) within 2 months prior to starting IO compared to no prior ATB (panel A), patients receiving ATB during IO compared to no ATB during IO (panel B), patients receiving ATB within 1 months after discontinuing IO compared to no ATB after IO (panel C) and patients receiving ATB prior and during IO compared to no ATB prior or during IO (panel D). HR = hazard ratio (TIFF 1332 kb)

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Schett, A., Rothschild, S.I., Curioni-Fontecedro, A. et al. Predictive impact of antibiotics in patients with advanced non small-cell lung cancer receiving immune checkpoint inhibitors. Cancer Chemother Pharmacol 85, 121–131 (2020). https://doi.org/10.1007/s00280-019-03993-1

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  • DOI: https://doi.org/10.1007/s00280-019-03993-1

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