Impact of nivolumab monotherapy infusion time-of-day on short- and long-term outcomes in patients with metastatic gastric cancer

Background: Immune checkpoint inhibitors are used either as monotherapy or in combination with cytotoxic agents in metastatic gastric cancer (mGC). Studies show that circadian rhythms are essential for immune system functions, including anticancer immunity. Objectives: This study evaluated whether the time of day of nivolumab infusion altered the efficacy of mGC treatment. Design: This was a retrospective cohort study. Methods: We retrospectively analyzed the data of 296 consecutive patients with mGC who received nivolumab monotherapy between December 2014 and December 2022. Patients were divided into early (EA)- and late (LA)-nivolumab infusion groups: the EA and LA groups received ⩾70% and <70% of their infusions before 14:00, respectively. Treatment efficacy was compared between the groups. Results: A total of 248 patients were eligible: 140 and 108 in the EA and LA groups, respectively. Most baseline characteristics were similar between the groups, except for differences in the neutrophil-to-lymphocyte ratio. The progression-free survival (PFS) and overall survival (OS) were significantly better in the EA than in the LA group (median PFS, 2.3 vs 1.6 months; hazard ratio (HR), 0.65; p < 0.01; median OS, 7.6 vs 3.9 months; HR, 0.64; p < 0.01). In multivariate analyses, EA was an independent prognostic factor for PFS (adjusted HR, 0.70; p < 0.01) and OS (adjusted HR, 0.67; p < 0.01). Immune-related adverse events were more frequent in the EA than in the LA group (40.7% vs 29.6%, p = 0.07). Conclusion: Our data suggest that scheduling nivolumab infusions before mid-afternoon should be considered in daily practice for the treatment of mGC.