Association between immunotherapy timing and efficacy in non-small cell lung cancer: a comprehensive analysis at a high-volume specialist centre.

Background: The timing of immune checkpoint inhibitor (ICI) administration may influence clinical outcomes in non-small cell lung cancer (NSCLC) patients. Previous studies have shown varying effects of chronotherapy on survival rates, with some suggesting that a higher percentage of doses administered in the morning improves overall survival (OS) and progression-free survival (PFS). This study aimed to evaluate the impact of the timing of the first dose and the percentage of doses administered in the afternoon on survival outcomes in advanced NSCLC patients, as well as explore seasonal variations. Methods: We conducted a retrospective cohort study at a tertiary cancer centre of patients diagnosed with NSCLC and programmed cell death ligand 1 (PD-L1) expression ≥50% who received first-line palliative treatment with pembrolizumab or atezolizumab. Patients were categorized based on the timing of their first dose (before or after 14:30) and further stratified by the percentage of doses received after 14:30. To evaluate seasonal variance, patients were also stratified into two groups: those who received their first dose within three months before or after the winter solstice ("Winter group") and those who received it within three months before or after the summer solstice ("Summer group"). Survival analysis was conducted using the Kaplan-Meier method. Results: We identified 349 patients who met the inclusion criteria. There was no significant difference in PFS or OS between patients receiving their first ICI dose before 14:30 (n=188) and those receiving it after 14:30 (n=161). However, a significant difference in OS was observed in patients who received more than 50% of their doses in the afternoon. Seasonal variations in dosing timing did not significantly impact survival outcomes. Conclusions: Our study suggests that the timing of the first ICI dose does not significantly affect survival outcomes in advanced NSCLC patients. However, patients receiving a higher percentage of their doses in the afternoon may experience poorer OS. Further prospective research is needed to confirm these findings and understand the underlying mechanisms before any changes to clinical practice can be recommended.