Proton pump inhibitors and cancer treatments: Emerging evidence against coadministration

[Display omitted] •Cancer patients are polymedicated and are at risk of drug interactions.•Proton pump inhibitors decrease absorption of many TKIs and CDK 4/6 inhibitors.•They decrease the diversity in microbiome, decreasing efficacy of immunotherapies.•The Precautionary Principle is of interest until we have new contradictory data.•PPIs may be replaced in most cases by antacids or H2 blockers. Proton pump inhibitors (PPIs) are widely used in cancer patients despite accumulating data showing that they can impact the efficacy of major anticancer drugs. This is particularly important with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (CPIs). Most TKIs require gastric acidity for their absorption and some retrospective series demonstrated that coprescription decreases the survival benefit of some TKI use (erlotinib, gefitinib and pazopanib). Relations between microbiota, the immune system, and the efficacy of immunotherapy are now obvious, just as modifications to gut flora after PPIs use are well-known. Many retrospective articles, including articles based on individual-participant data from randomized studies, demonstrated that patients treated with CPIs have a poorer outcome (overall survival, progression-free survival and response rate) when they received PPIs concomitantly, while there was no impact of such coprescription among patients in control arms, not treated with immunotherapies. Similar data were also observed in patients treated with palbociclib. For these interactions, it is very important to use the precautionary principle and warn patients and physicians about this. In patients who require acid suppression because of severe symptoms, using antacids or H2 blockers could be recommended.