Association Between Administration Timing and Efficacy of Nivolumab in Non-small Cell Lung Cancer Treatment

Circadian rhythms modulate immune function and may influence the efficacy of immune checkpoint inhibitors (ICIs). In small-scale studies, morning administration of ICIs has improved outcomes in patients with non-small cell lung cancer (NSCLC). This multicenter retrospective study evaluated the association between ICI administration timing and clinical outcomes in patients with NSCLC treated with nivolumab.

We retrospectively analyzed patients with metastatic NSCLC receiving ≥3 courses of nivolumab monotherapy as second- or later-line therapy at two institutions. Patients were stratified into morning (≥2 infusions before 11:00) and afternoon (≥2 infusions after 11:00) groups based on the timing of their first three administrations. Overall survival (OS), progression-free survival (PFS) and tumor response were analyzed according to timing group.

Among the 257 patients, 51 (19.8%) received morning and 206 (80.2%) afternoon administration. Median OS was significantly longer in the morning group [21.3 vs. 13.8 months; hazard ratio (HR)=0.64, 95% confidence interval (CI)=0.45-0.92; p=0.015]. PFS favored morning administration (6.54 vs. 4.21 months; HR=0.77, 95%CI=0.55-1.06; p=0.11). Multivariate analysis showed a non-significant trend favoring morning administration for OS (HR=0.75, 95%CI=0.52-1.09; p=0.14).

Morning nivolumab administration may be associated with improved OS in patients with NSCLC. Prospective studies are warranted to clarify the clinical relevance of infusion timing and its possible contribution to treatment outcomes.