Impact of infusion timing (IT) on survival outcomes across gastrointestinal (GI) malignancies: A multicenter analysis of circadian rhythm (CR) effects on immune checkpoint inhibitor (ICI) activity.

837 Background: A recent randomized trial suggested that CR may influence ICI activity in patients with lung cancer. However, the same has not been established in GI cancers, where reports have shown mixed results with variable definitions of 'early' vs 'late' IT. We evaluated multiple approaches to assess the impact of CR on first-line ICI in GI malignancies. Methods: This retrospective study included patients from three Mayo Clinic sites (N=455). Both previously reported IT cutoffs and a new cutoff derived from ROC analysis were evaluated. Patients were categorized by the median of all ITs, the median of the first four ITs, and whether ≥20% of ITs occurred before the identified cutoff. Univariate and multivariate Cox regression (adjusting for age, MSI status, type of cancer, metastasis status, number of cycles, and receipt of chemotherapy with ICI) assessed associations with OS. KM analyses were performed to illustrate survival differences. The primary endpoint was OS. Results: When patients were categorized based on whether ≥20% of infusions occurred before 14:00 (ROC-derived cutoff), a significant association with OS was observed. On univariate analysis, early infusion timing was associated with improved survival (HR 2.30, 95% CI 1.58–3.32, p