Immune checkpoint inhibitors (ICIs) have been shown to improve patients’ clinical outcomes in a variety of cancers, but with variable efficacy. Prior research has also suggested that systemic antibiotic (ABX) exposure may impact the intestinal microbiota and result in suboptimal ICI treatment outcomes. Six meta-analyses studying the progression-free survival (PFS) and overall survival (OS) of cancer patients treated with ICIs and exposed to ABX were published between 2019 and 2020. The present abstract aims at updating those meta-analyses by incorporating all new studies that have been published up to September 2020.
Medline (through PubMed), the Cochrane Library and major oncology conferences proceedings were systematically searched to identify studies assessing the impact of ABX use on the clinical outcomes of cancer patients treated with ICIs. Studies were found eligible for inclusion when they mentioned Hazard Ratios (HRs) or Kaplan–Meier curves for OS or PFS based on antibiotic exposure. Pooled HRs for OS and PFS as well as HRs for OS and PFS according to cancer type and to ABX exposure time window were calculated.
Eligible results from 70 independent cohorts were published between 2018 and September 2020 and included in this meta-analysis. Altogether, 63 independent cohorts reported data for OS (22,977 patients) and 45 for PFS (14,547 patients). The pooled HR was 1.65 (95% confidence interval [CI]: 1.46-1.88) for OS and 1.44 (95% CI: 1.27-1.64) for PFS, confirming a significantly reduced survival in patients with cancer exposed to ABX. The detailed analysis in subgroups based on the exposure time window suggests that the deleterious effect of ABX is stronger when the exposition happens shortly before and after the start of the ICI treatment.
This update of meta-analyses confirms the previously reported deleterious effect of ABX on ICI treatment outcomes, taking into account the latest publications in the field. The topic deserves further research to uncover if the effect will stand with 1st line use of ICI together with chemotherapies and/or other approved combinations, elucidate the mechanisms at stake and improve care of patients.
Legal entity responsible for the study
G. Zalcman: Advisory/Consultancy: Da Volterra. A. Crespin: Full/Part-time employment: Da Volterra. J. Cervesi: Full/Part-time employment: Da Volterra. C. Le Bescop: Shareholder/Stockholder/Stock options, Full/Part-time employment: Da Volterra. R. Buffet: Full/Part-time employment: Da Volterra. J. De Gunzburg: Advisory/Consultancy, Shareholder/Stockholder/Stock options, Officer/Board of Directors: Da Volterra. P-A. Bandinelli: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Da Volterra.