Impact of earlier time of first cycle immunotherapy administration on progression-free survival in real-world metastatic non–small cell lung cancer.

Abstract

e20579 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). Recent evidence suggests that earlier time of day (ToD) ICI administration is associated with improved clinical outcomes across multiple cancer types, implicating circadian regulation of immune function in immunotherapy efficacy. Data in NSCLC, particularly from real-world and racially and ethnically diverse populations, remain limited. We investigated the association between ToD of immunotherapy administration and survival outcomes in a racially and ethnically diverse population with metastatic NSCLC. Methods: We conducted a retrospective cohort study of patients with Stage IV NSCLC treated with ICIs between 2014 and 2025. Time of day of the first ICI infusion was extracted from infusion start times. Patients were stratified into earlier and later ToD groups using median, tertile, and quartile cutoff analyses. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods and Cox proportional hazards models adjusted for age, sex, race/ethnicity, ECOG performance status, histology, PD-L1 expression, and socioeconomic status. Results: A total of 215 patients were included. 42% were Black, 30% Hispanic, and 28% Caucasian/Asian. Late ToD group was defined as ≥11:30 am for the median analysis, ≥2:30 pm for the tertile analysis, and ≥3:02 pm for the quartile analysis. PFS and OS did not differ significantly by race or ethnicity. Later time of ICI administration was associated with inferior PFS across median (adjusted HR 1.46, 95% CI 1.04-2.04, p=0.028), quartile (HR 1.87, 95% CI 1.17-2.98, p=0.0009), and tertile (HR 1.95, 95% CI 1.3-2.92, p=0.001) analytic groups when compared with earlier administration. A non-significant trend toward improved OS with earlier ToD administration was observed. ECOG performance status ≥2 was independently associated with poorer PFS and OS across all groups. Higher socioeconomic distress, measured by patient zip codes and the Distressed Communities Index, was independently associated with poorer OS in both univariate and multivariate analysis. Conclusions: In this real-world study of metastatic NSCLC, earlier first-cycle ICI administration was associated with significantly improved PFS and a consistent trend toward improved OS, regardless of race or ethnicity. Performance status and socioeconomic distress were also independently associated with survival outcomes. These findings suggest that the circadian timing of ICI administration may impact immunotherapy efficacy, warranting further investigation of chronotherapy-informed ICI administration.