Background: Circadian rhythms influence immune function and may affect efficacy of immune checkpoint inhibitors (ICIs). Some published studies suggest early time-of day ICI administration may be associated with better survival outcomes.
Aim: To evaluate the impact of time-of-day ICI administration on overall survival (OS) and progression free survival (PFS).
Methods: A multicentre retrospective study was conducted of patients who commenced first-line ICI monotherapy between 01/01/2020 and 31/12/2024. Treatments included avelumab, ipilimumab-nivolumab, nivolumab, nivolumab-relatlimab or pembrolizumab for advanced melanoma, Merkel cell carcinoma, renal cell carcinoma or squamous cell carcinoma. Patients were identified through prescribing systems with data collected using medical records. Kaplan-Meier curves and log-rank tests were used to compare OS and PFS in time-of-day administration (before versus after 2pm). Cox regression evaluated independent effects, adjusting for age, sex, performance status, cancer type and stage, presence of brain metastases, and lactate dehydrogenase.
Results: Of the 360 patients included, after adjustment for clinical and disease-related factors, no significant association was observed for OS between the infusion time after 2pm for the first treatment cycle (HR 0.88, 95% CI 0.53–1.46, p = 0.614) and the median of all cycles (HR 1.44, 0.83-2.51, p= 0.198). Regarding PFS, no significant association was observed between the infusion time after 2pm for the first cycle (HR 0.79, 95% CI 0.46–1.36, p=0.390) or median of all cycles (HR 0.99, 95% CI 0.54–1.82, p=0.981).
Conclusions: ICI administration after 2pm was not associated with worse OS and PFS. This study suggests the association between time-of-day administration and outcomes remain inconclusive. Inconsistencies may potentially be attributable to unaddressed confounding factors, such as concomitant medicines use on ICI efficacy or scheduling factors. Prospective, randomised trials addressing potential confounders are needed to clarify the impact of time-of-day treatment on survival outcomes.