Systematic review and meta-analysis of optimizing timing of immune checkpoint inhibitors for advanced solid tumors

Emerging evidence from observational studies suggests that time-of-day of immune checkpoint inhibitor (ICI) infusion may influence efficacy. Systematic review and meta-analysis of articles published before April 2026 evaluated the impact of ICI infusion timing on outcomes of patients with advanced solid tumors. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Forty-three retrospective cohort studies involving 11,941 patients were included. Pooled analysis revealed a significant association between early time-of-day infusion and improved OS (HR 0.60; 95% CI 0.53-0.67) and PFS (0.65; 0.57-0.73); ORR was also higher with early time-of-day infusion (RR 1.37; 95% CI 1.21-1.54). No significant differences were observed for any-grade immune-related adverse events (RR 0.98; 95% CI 0.73-1.32) or grade ≥ 3 irAEs90.95; 0.62-1.46). However, significant publication bias was detected (Eggre’s test p<0.001); after trim-and-fill adjustment, the OS association remained significant (aHR 0.79; 95% CI 0.71-0.89), whereas PFS association was attenuated (0.89; 0.79-1.00). The authors conclude that this meta-analysis suggests a significant association between early time-of-day ICI adminstration and improved outcomes; these findings must be interpreted with caution, as the evidence base is composed entirely of observational studies with inherent risk of bias, and the presence of publication bias may have led to overestimation of the observed effect size (graphical abstract).