Baseline co-medications may alter the anti-tumoural effect of checkpoint inhibitors as well as the risk of immune-related adverse events

• DOI: 10.1016/j.ejca.2021.08.036
• Publication Date: 2021-10-13T04:36:46Z
• Authors: Marie Kostine; Eleonora Mauric; Alice Tison; Thomas Barnetche; Aurélien Barre; Macha Nikolski; Léa Rouxel; Caroline Dutriaux; Léa Dousset; Sorilla Prey; Marie Beylot-Barry; Julien Seneschal; Rémi Veillon; Charlotte Vergnen...; Amaury Daste; Charlotte Domblides; Baptiste Sionneau; Marine Gross-Goupil; Alain Ravaud; Edouard Forcade; Thierry Schaeverbeke
• Keywords: Male; 0301 basic medicine; Prescription Drugs; Angiotensin-Converting Enzyme Inhibitors; Comorbidity; Middle Aged; Gastrointestinal Microbiome; 3. Good health; Angiotensin Receptor Antagonists; 03 medical and health sciences; Neoplasms; Humans; Drug Interactions; Female; [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]; Immune Checkpoint Inhibitors; Response Evaluation Criteria in Solid Tumors; Aged; Neoplasm Staging; Retrospective Studies

As gut microbiota composition is an important determinant of response to immune checkpoint inhibitors (ICIs), we examined the effect of various co-medications known for their interaction with microbiota, when given at ICI initiation.We identified patients with advanced cancer treated with ICI between May 2015 and September 2017 in our institution. Co-medications given within 1 month before or 1 month after the first administration of ICI were reviewed from medical records. Survival data were analysed with univariable Cox regression, and the combined effect of multiple factors was assessed with factor analysis of mixed data (FAMD). The impact of co-medications on immune-related adverse events (irAEs) occurrence was also assessed.A total of 635 patients were included. Psychotropic drugs (41%), proton pump inhibitors (PPIs; 38%), angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARBs; 32%), glucocorticoids (26%), antibiotics (24%), statins (21%) and morphine (20%) were the most prescribed co-medications. Baseline use of antibiotics, glucocorticoids >10 mg/day, PPIs, psychotropic drugs, morphine and insulin was associated with significantly shortened overall survival and decreased tumour response, whereas coadministration of statins, ACEs and/or ARBs, non-steroidal anti-inflammatory drugs, aspirin and oral antidiabetic drugs did not impact patient outcomes. Treatments that altered the response to ICI were also associated with a decreased incidence of irAEs. FAMD revealed the respective weight of each factor or co-medication on the oncological outcomes.Co-medications must be carefully assessed at the time of ICI initiation and clinicians aware of their possible deleterious effect, notably for PPIs, glucocorticoids, antibiotics and psychotropic drugs.