ASCO-SITC 2019—Antibiotics in prior month tied to reduced ICI efficacy


  • Melissa Pandika
  • Univadis
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Takeaway

  • Antibiotic therapy 1 month prior to, but not concurrently with, immune checkpoint inhibition (ICI) was associated with shorter OS, higher likelihood of primary refractoriness to ICI in patients regardless of tumor type.  

Why this matters

  • Points to antibiotic-induced gut dysbiosis as possible prognostic marker, actionable driver of antitumor immune response.
  •   Raises question of whether clinicians should reestablish healthy gut microbiome prior to ICI.
  • Suggests timing of antibiotic therapy is crucial to its effect on ICI.

Study design

  • Observational study prospectively maintained data set of 196 ICI-treated patients with NSCLC, melanoma, other histotypes.
  • Documented timing, duration of antibiotic therapy (ATB) given within ~30 days prior to ICI (pATB) or concurrently (cATB) until ICI cessation.
  • Evaluated OS, response.

Key results

  •   pATB associated with worse OS (P<.001 hr>
    • pATB OS: 2 months.
    • No pATB OS: 26 months.
  • No association between cATB, OS (P=.76).
  • pATB associated with higher likelihood of primary progressive disease (PD, P<.001>
    • pATB PD: 81%.
    • No pATB PD: 44%.

Limitations

  • Retrospective study.
  • Unclear if antibiotic use a surrogate for other poor-risk patient factors or if results independent of other biomarkers (e.g., IFNγ, PD-L1).  
  • Possible that ATB