Abstract 1043P
Background
Immune checkpoint inhibitors (ICI) have improved patient outcomes in a variety of cancers but with variable efficacy. In the past 24 months, several observational studies, mostly retrospective, suggested that antibiotic (ABX) use may be associated with a lowered efficacy of ICI and survival of patients. ABX-induced disruption of the gut microbiota and the complex interplay between the immune system and the microbiota have been advanced as the likely mechanisms underlying the observed effect. We aim at reviewing the meta-analyses that summarized the findings reported in literature.
Methods
We systematically searched Medline, the Cochrane Library, and oncology conferences proceedings to identify the systematic reviews and meta-analyses as well as all the recent studies that were not included in them.
Results
We identified 4 meta-analyses published since 2019 studying the overall survival (OS) and progression-free survival (PFS) of cancer patients treated with ICI (mainly anti-PD(L)1 antibodies as monotherapy or combined with anticancer drugs) and ABX. In all, ABX use is reported to have a negative impact on the survival of patients treated with ICI regardless of cancer type. The pooled hazard ratio (HR) ranged from 1.47 to 1.84 for PFS and 1.69 to 2.37 for OS, revealing a significantly reduced survival in patients with cancer exposed to ABX. In all meta-analyses, the use of ABX around the ICI treatment start appeared to be most detrimental to the outcomes. Table: 1043P
| 1st Author | Huang | Wilson | Lurienne | Xu |
| Cancer | Non-small-cell lung cancer (NSCLC), Melanoma, Renal cell carcinoma (RCC), Urothelial Carcinoma (UC), Mixed | NSCLC, Melanoma, RCC, UC, Mixed | NSCLC | NSCLC, Melanoma, RCC, Mixed |
| HR OS [95% CI] | 2.37 [2.05; 2.75] | 1.92 [1.37; 2.68] | 1.69 [1.25; 2.29] | 1.90 [1.55; 2.34] |
| HR PFS [95% CI] | 1.84 [1.49; 2.26] | 1.65 [1.30; 2.10] | 1.47 [1.13; 1.90] | 1.53 [1.30; 1.79] |
Conclusions
The independently-developed meta-analyses vary in the scope of studies included and their methodology but they commonly conclude on a significant deleterious effect of ABX use on the survival of patients treated with ICI. The topic deserves further research to understand the mechanisms at stake and improve care of patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Da Volterra.
Funding
Da Volterra.
Disclosure
J. Cervesi, A. Crespin: Full/Part-time employment: Da Volterra. R. Buffet: Advisory/Consultancy: Da Volterra. J. de Gunzburg: Advisory/Consultancy, Shareholder/Stockholder/Stock options, Officer/Board of Directors: Da Volterra. G. Zalcman: Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies, PI of the phase III MAPS trial. ASCO meeting 2016 & 2017 attendance: Roche; Advisory/Consultancy, Advisory Board: MSD; Advisory/Consultancy, Non-remunerated activity/ies, ESMO meeting 2019 attendance: BMS; Advisory/Consultancy, Non-remunerated activity/ies, Advisory board and preclinical research grant (ANR): Inventiva; Non-remunerated activity/ies, ASCO meeting 2015 attendance: Pfizer; Advisory/Consultancy, Non-remunerated activity/ies, ASCO meeting 2019 & ESMO meeting 2018 attendance. Advisory board: AstraZeneca; Non-remunerated activity/ies, ASCO meeting 2018 attendance: Abbvie; Non-remunerated activity/ies, PI of an observational multi-center study on ABX use in patients treated by ABX: Da Volterra. P-A. Bandinelli: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Da Volterra.