The Negative Impact of Antibiotics on Outcomes in Cancer Patients Treated With Immunotherapy

A New Independent Prognostic Factor?

A. Elkrief; L. Derosa; G. Kroemer; L. Zitvogel; B. Routy

Disclosures

Ann Oncol. 2019;30(10):1572-1579. 

In This Article

Discussion

Taken together, 11 out of the 12 studies suggest a negative impact of ATBs on clinical outcome of patients with NSCLC, RCC or melanoma who are treated with ICIs targeting either PD-1 or PD-L1. Although compelling, the retrospective nature of these studies limits the strength of the conclusions. At this time, several questions remain unanswered. For example, none of the 12 studies took into account possible modulators of the gut microbiota such as diet, geography or other co-medications than ATBs that might constitute confounding factors. At this point, the present systematic review suggests that the timing of broad-spectrum antibiotic treatments with respect to the initiation of ICI-based immunotherapy is important. Thus, treatment with broad-spectrum ATBs during the month before the commencement of immunotherapy appears particularly deleterious, more so than when ATBs have been administered before. However, many other questions remain unanswered. Should patients treated with a short-course antibiotherapy be included in the ATB-treated group? What is the minimum duration of ATB therapy that should be taken into account? And is it important to distinguish broad-spectrum combination ATB treatments from single-agent and short-course antibiotherapies, especially if they involve narrow-spectrum ATB? Are there ATBs that are particularly negative for clinical outcome? Or on the contrary, are there perhaps specific ATBs that might induce favorable alterations in the host immune system? At this point, the clinical data that are available are not sufficient to provide clear answers to all these questions.

Beyond the firm recommendation to use ATB judiciously, more robust, prospective data are required to elaborate guidelines for the optimal management of patients who do require ATBs shortly before or while on ICI. For example, more data are required to determine whether postponing the initiation of ICI-based immunotherapy would allow a spontaneous recovery from ATB-mediated dysbiosis, thus improving the efficacy of the treatment. However, this approach may be unrealistic for patients with an elevated tumor burden, where prompt ICI initiation is required. In this arena, clinical trials are currently underway to evaluate the utility of targeted interventions designed to rapidly revert ATB-induced dysbiosis, for instance by FMT, prebiotics and probiotics.

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