Comedications with Immune Checkpoint Inhibitors: Involvement of the Microbiota, Impact on Efficacy and Practical Implications

SIMPLE SUMMARY: Since the approval of immune checkpoint inhibitors for solid tumors, concerns have been raised about the role of the microbiota on immunotherapy success and the potential negative impact of several drugs on oncological response and survival. In this review, we analyzed the existing data regarding such negative but also positive effect of many drugs on immunotherapy results. Most deleterious drugs concerning immunotherapy efficacy are corticosteroids, antibiotics and proton pump inhibitors, but preclinical as well as clinical studies have been conducted on other molecules such as metformin, statins, aspirin or beta blockers. The aim of this review is to elaborate a practical overview of current scientific data to help clinicians make critical treatment decisions by taking into account the totality of their patients’ comedications. ABSTRACT: Immune checkpoint inhibitors (ICIs) have been a major breakthrough in solid oncology over the past decade. The immune system and the gut microbiota are involved in their complex mechanisms of action. However, drug interactions have been suspected of disrupting the fine equilibrium necessary for optimal ICI efficacy. Thus, clinicians are facing a great deal of sometimes contradictory information on comedications with ICIs and must at times oppose conflicting objectives between oncological response and comorbidities or complications. We compiled in this review published data on the role of the microbiota in ICI efficacy and the impact of comedications. We found mostly concordant results on detrimental action of concurrent corticosteroids, antibiotics, and proton pump inhibitors. The timeframe seems to be an important variable each time to preserve an initial immune priming at ICIs initiation. Other molecules have been associated with improved or impaired ICIs outcomes in pre-clinical models with discordant conclusions in retrospective clinical studies. We gathered the results of the main studies concerning metformin, aspirin, and non-steroidal anti-inflammatory drugs, beta blockers, renin-angiotensin-aldosterone system inhibitors, opioids, and statins. In conclusion, one should always assess the necessity of concomitant treatment according to evidence-based recommendations and discuss the possibility of postponing ICI initiation or switching strategies to preserve the critical window.