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Study Updating Meta-analysis Confirms the Deleterious Effect of Systemic Antibiotics on Immune Checkpoint Inhibitor Efficacy

Previously reported findings suggest that systemic antibiotic exposure may alter the efficacy of treatment with an immune checkpoint inhibitor by impacting the intestinal microbiota
09 Dec 2020
Cancer Immunology and Immunotherapy

An update of meta-analyses confirmed previous reports of poorer outcomes following immune checkpoint inhibitor (ICI) treatment in patients exposed to systemic antibiotics. Researchers reported at the ESMO Immuno-Oncology Virtual Congress 2020, held from 9 to 12 December 2020, that the deleterious impact upon ICI treatment was strongest with antibiotic used that occurred directly prior to or immediately after the initiation of ICI therapy.

Gérard Zalcman of the Department of Thoracic Oncology and CIC1425, Hôpital Bichat-Claude Bernard, Assistance Publique Hôpitaux de Paris, Université de Paris in Paris, France, presented an update of systematic reviews and meta-analyses studying the association between antibiotic exposure, progression-free survival (PFS) and overall survival (OS) in cancer patients treated with ICIs.

The updated meta-analysis included all new studies published up to October 2020 that were identified by searching Medline, the Cochrane Library and major oncology conferences’ proceedings. Studies were included when they assessed the impact of antibiotic use on the clinical outcomes of patients treated for cancer with ICIs and provided hazard ratios (HRs) or Kaplan–Meier curves for OS or PFS based upon antibiotic exposure. Pooled HRs for OS and PFS were calculated according to cancer type and the time window of antibiotic exposure.

The database search uncovered data from 70 independent cohorts that were published from 2018 to October 2020 and included in the meta-analysis. Of these, 65 independent cohorts reported OS data representing 23,146 patients and 45 cohorts provided PFS results for 14,689 patients.

The OS (pooled HR 1.65; 95% confidence interval [CI] 1.46-1.87) and PFS (pooled HR 1.44; 95% CI 1.27-1.64) data from these cohorts confirmed that survival was significantly decreased in patients receiving ICIs for cancer who were also exposed to antibiotics.

The investigators also performed a detailed analysis in subgroups based on the cancer type and on the antibiotic exposure time window. These findings suggest that the deleterious effect of antibiotics is greatest for non-small-cell lung carcinoma and melanoma and when the exposure occurs shortly before and after the start of the ICI treatment.

Study-Updating-Meta-analysis-Confirms-the-Deleterious-Effect-of-Systemic-Antibiotics-on-Immune-Checkpoint-Inhibitor-Efficacy

Antibiotic exposure time window.

© Gérard Zalcman.

Conclusions

The authors of this poster concluded that this work confirmed the previously reported deleterious effect of antibiotic use on ICI treatment outcomes, taking into account the latest publications in the field.

They advise that this issue warrants further research to uncover if the effect will stand with first-line line use of ICI together with chemotherapies and/or other approved combinations, and to elucidate the mechanisms at stake, as well as to improve patient care.

Funding from Da Volterra was disclosed.

Reference

50P – Zalcman G, Crespin A, Cervesi J, et al. Update of systematic reviews and meta-analyses studying the association between antibiotic use and clinical outcomes of cancer patients treated with immune checkpoint inhibitors. ESMO Immuno-Oncology Virtual Congress 2020 (9-12 December).

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