Early time-of-day infusion of PD-1 inhibitor improves prognosis in advanced gastric cancer: a multicenter real-world study

Background Whether the time-of-day administration (ToDA) of programmed cell death 1 (PD-1) inhibitor infusion influences survival in advanced gastric cancer (AGC) remains unclear. This research aimed to evaluate the impact of ToDA on the prognosis of AGC patients. Methods This multicenter retrospective study enrolled 416 AGC patients receiving PD-1 inhibitor therapy, who were divided into early and late ToDA groups based on sensitivity analyses using 30-minute intervals of the administration time window. After 1:2 propensity score matching (PSM), progression-free survival (PFS) and overall survival (OS) were compared between groups, and subgroup analyses were conducted. Subsequently, prognostic risk score models were established based on independent prognostic factors. Results A cutoff time of 15:00 was established via sensitivity analyses in the overall cohort. Patients were categorized into early and late ToDA groups. After PSM, multivariable Cox analyses identified late ToDA as an independent risk factor for both PFS ( P < 0.001) and OS ( P = 0.004). Kaplan–Meier curves demonstrated significantly better PFS ( P = 0.003) and OS ( P = 0.003) for the early ToDA group. In the overall cohort, prognostic risk score models incorporating ToDA, metastasis sites, treatment lines, neutrophil-to-lymphocyte ratio (NLR), human epidermal growth factor receptor 2 (HER-2) status and programmed cell death ligand 1 (PD-L1) status effectively stratified patients into low-, middle-, and high-risk groups with distinct survival ( P < 0.001). The detrimental effect was observed across most major subgroups, though several subgroup analyses were not statistically significant. Conclusions This research provides real-world evidence that early ToDA of PD-1 inhibitors is associated with improved prognosis in AGC patients, providing a rationale for chronotherapy optimization and introducing a preliminary risk stratification model for AGC immunotherapy. The risk scoring model requires prospective validation.