Cancer: prior antibiotics cut response to immune checkpoint inhibitors

  • Pinato DJ & al.
  • JAMA Oncol
  • 12/09/2019

  • Yael Waknine
  • Clinical Essentials
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Takeaway

  • Recent antibiotic therapy (within 30 days) is associated with poorer response to cancer immune checkpoint inhibitors (ICI), translating to shorter survival regardless of tumor site.

Why this matters

  • Broad-spectrum antibiotics can cause gut dysbiosis, impairing response to ICI therapy.

Study design

  • Prospective study of 196 patients with cancer (69.9% men; median age, 68 years) receiving checkpoint inhibitors at 2 tertiary academic referral centers from January 2015 to January 2018.
  • Funding: Imperial College National Institute for Health Research Biomedical Research Center; Imperial College Tissue Bank; Imperial Cancer Research UK Center.  

Key results

  • Most had NSCLC (60.7%) or melanoma (19.4%).
  • Prior vs no antibiotic therapy was tied to poorer OS (2 vs 26 months; HR, 7.4; P<.001 by cancer type these os values were: style="list-style-type:circle;">
  • NSCLC: 2.5 vs 26 months (P<.001>
  • Melanoma: 3.9 vs 14 months (P<.001>
  • Other tumor types: 1.1 vs 11 months (P<.001>
  • No association was found for current antibiotic therapy (P=.65).
  • Prior antibiotic therapy was linked to higher likelihood of ICI-refractory disease (81% vs 44%; P<.001 defined as progression within weeks of first dose.>
  • Multivariate analysis supported prior antibiotic therapy (HR, 3.4; P<.001 and poor response to ici therapy as predictors of os independent tumor site disease burden performance status.>

    Limitations

    • No data on gut microbiota.
    • Small sample size.