Trial in Progress (TiP): The FOod intervention trial to Reduce immunotherapy toXicity (FORX)

Background: Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment but can cause immune related adverse events (irAEs) which we currently do not know how to prevent. These irAEs influence patients’ quality of life and oncological treatment course. The gut plays an essential role in immune homeostasis and gut dysbiosis is implicated in (auto)inflammatory conditions. The American Gut project, an international microbiome study, showed that healthy volunteers who ingested at least 30 different plants (vegetables, fruits, nuts) weekly had a more diverse microbiome than those who consumed 10 or less. A fibre-rich diet has been associated with improved outcome of ICI treatment.

Trial design: The FORX trial investigates whether altering the composition of the gut microbiome can improve ICI tolerance. In our tertiary reference centre, we are supplementing the diets of solid tumour patients with weekly boxes containing 30 different plants during the first 12 weeks of their ICI treatment. The increased fibre intake is expected to strengthen the gut microbiome and reduce the incidence of irAEs. Stool and blood samples will clarify the microbial and cytokine signatures associated with irAEs. Baseline physical activity and body composition are assessed given recent retrospective data showing synergistic effects of exercise, body composition and ICI therapy. Quality of life questionnaires are completed at baseline, week 6 and week 12 throughout the intervention. The FORX trial is the first prospective trial to investigate a concrete dietary adaptation. Our trial will provide valuable insights in the interaction between the gut microbiome, physical fitness and autoimmunity and serve as a basis for nutritional and probiotic advice. It will empower cancer patients and improve their quality of life. Recruitment started in January 2024 and until now 27/60 patients have been enrolled.