Real-world impact of first immunotherapy infusion timing on outcomes in locally advanced non-small cell lung cancer.

Abstract

8071 Background: Emerging evidence suggests that earlier time-of-day (ToD) infusion of immune checkpoint inhibitors (ICIs) is associated with improved progression-free survival (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). Although the timing of the initial infusion may be particularly influential, its impact on outcomes in earlier stages of NSCLC remains unclear. We investigated the association between first ICI infusion ToD and clinical outcomes in a racially and ethnically diverse population with locally advanced NSCLC. Methods: We conducted a retrospective cohort study of patients with locally advanced NSCLC treated with definitive chemoradiation followed by consolidation durvalumab between 2018-2025. Patient demographics, smoking status, ECOG performance status, PD-L1 tumor proportion score (TPS), lung cancer stage and histology, disease volume (DV), mean heart dose, and clinical outcomes were all obtained using chart review. Neighborhood distress was classified using patient zip codes and the Distress Communities Index. ICI administration timing was categorized into quartiles: ≤11:20 AM, 11:20 AM-12:32 PM, 12:32 PM-13:48 PM, >13:48 PM. Kaplan Meier methods and cox proportional hazards models, adjusted for major patient factors, were used to evaluate OS and PFS. Results: Among 109 eligible patients (median age 69.5 years), 55% were male, 42% were Non-Hispanic Black, 30% were Hispanic, 64% resided in distressed ZIP codes. Patients receiving ICIs in the latest ToD quartile (>13:48) had a significantly shorter PFS compared to those treated in the earliest quartile (≤11:20) in both univariate (HR 2.10, p=0.024) and multivariate analysis (HR 3.32, p=.0.0057). A non-significant trend towards inferior OS was also observed with later ToD administration. Higher DV (HR 1.09 per 10 mL, p=0.029) and mean heart dose (HR 1.86, p=0.03) were independently associated with worse OS. Conclusions: In this real-world study of a diverse population with locally advanced NSCLC, later ToD ICI administration (>13:48) was associated with a significantly shorter PFS and a trend towards worsened OS. These findings suggest that the timing of ICI delivery may influence outcomes in locally advanced NSCLC, consistent with prior observations in metastatic disease, and highlight the need for prospective trials to validate the impact of infusion timing on survival and clarify the underlying circadian mechanisms contributing to these differences. Multivariable Cox regression analysis. OS PFS HR 95% CI p-value HR 95% CI p-value ToD of First Infusion ≤11:20 - - - - - - 11:20-12:32 1.53 0.57,4.10 0.40 1.68 0.75,3.80 0.21 12:32-13:48 0.48 0.15,1.59 0.23 1.30 0.53,3.16 0.57 >13:48 1.66 0.62,4.45 0.31 3.32 1.39,7.92 0.007 Mean Heart Dose (Gy) 1.86 1.06,3.26 0.030 1.54 0.98,2.42 0.060 Disease Volume (mL) 1.09 per 10 mL 1.01,1.17 0.029 1.03 per 10 mL 0.97,1.09 0.29