Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer Journal Article


Authors: Derosa, L.; Hellmann, M. D.; Spaziano, M.; Halpenny, D.; Fidelle, M.; Rizvi, H.; Long, N.; Plodkowski, A. J.; Arbour, K. C.; Chaft, J. E.; Rouche, J. A.; Zitvogel, L.; Zalcman, G.; Albiges, L.; Escudier, B.; Routy, B.
Article Title: Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer
Abstract: Background: The composition of gut microbiota affects antitumor immune responses, preclinical and clinical outcome following immune checkpoint inhibitors (ICI) in cancer. Antibiotics (ATB) alter gut microbiota diversity and composition leading to dysbiosis, which may affect effectiveness of ICI. Patients and methods: We examined patients with advanced renal cell carcinoma (RCC) and non-small-cell lung cancer (NSCLC) treated with anti-programmed cell death ligand-1 mAb monotherapy or combination at two academic institutions. Those receiving ATB within 30 days of beginning ICI were compared with those who did not. Objective response, progressionfree survival (PFS) determined by RECIST1.1 and overall survival (OS) were assessed. Results: Sixteen of 121 (13%) RCC patients and 48 of 239 (20%) NSCLC patients received ATB. The most common ATB were β-lactam or quinolones for pneumonia or urinary tract infections. In RCC patients, ATB compared with no ATB was associated with increased risk of primary progressive disease (PD) (75% versus 22%, P < 0.01), shorter PFS [median 1.9 versus 7.4 months, hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.4-6.9, P < 0.01], and shorter OS (median 17.3 versus 30.6 months, HR 3.5, 95% CI 1.1-10.8, P=0.03). In NSCLC patients, ATB was associated with similar rates of primary PD (52% versus 43%, P=0.26) but decreased PFS (median 1.9 versus 3.8 months, HR 1.5, 95% CI 1.0-2.2, P=0.03) and OS (median 7.9 versus 24.6 months, HR 4.4, 95% CI 2.6-7.7, P < 0.01). In multivariate analyses, the impact of ATB remained significant for PFS in RCC and for OS in NSCLC. Conclusion: ATB were associated with reduced clinical benefit from ICI in RCC and NSCLC. Modulatation of ATB-related dysbiosis and gut microbiota composition may be a strategy to improve clinical outcomes with ICI. © The Author(s) 2018.
Keywords: renal cell carcinoma; non-small-cell lung cancer; antibiotics; microbiota; immune checkpoint inhibitors
Journal Title: Annals of Oncology
Volume: 29
Issue: 6
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2018-06-01
Start Page: 1437
End Page: 1444
Language: English
DOI: 10.1093/annonc/mdy103
PROVIDER: scopus
PUBMED: 29617710
PMCID: PMC6354674
DOI/URL:
Notes: Article -- Export Date: 4 September 2018 -- Source: Scopus
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MSK Authors
  1. Jamie Erin Chaft
    200 Chaft
  2. Matthew David Hellmann
    339 Hellmann
  3. Niamh   Long
    16 Long
  4. Kathryn Cecilia Arbour
    54 Arbour
  5. Hira Abbas Rizvi
    89 Rizvi