Overall survival according to time‐of‐day of immunochemotherapy for extensive‐stage small cell lung cancer

BACKGROUND: Emerging evidence suggests that circadian timing influences the efficacy of immune checkpoint inhibitors (ICI), with morning infusions associated with improved therapeutic outcomes across various malignancies. However, the impact of ICI infusion timing on extensive-stage small cell lung cancer (ES-SCLC), a disease with poor prognosis and limited therapeutic advancements, remains unexplored. METHOD: This retrospective study (LungTime-R02) analyzed 397 patients with ES-SCLC who received first-line anti-PD-L1 (atezolizumab or durvalumab) plus chemotherapy at our center between May 2019 and October 2023. The time of day of administration (ToDA) was calculated as the median infusion time for each patient's first four ICI treatment cycles. To assess its prognostic relevance, hazard ratios (HRs) of earlier progression or death were estimated across multiple ToDA thresholds (11:00-16:30). Propensity score matching (1:2) was applied to balance baseline characteristics. RESULT: Of the 397 patients, the optimal ToDA cutoff for maximizing progression-free survival (PFS) benefit was identified as 15:00, with the lowest HR for PFS observed at this threshold. Patients who received immunochemotherapy before 15:00 exhibited significantly longer PFS and overall survival compared to those treated later, with results consistent across pooled and propensity score matching cohorts. Multivariable analysis confirmed early ToDA as an independent prognostic factor for both PFS (adjusted HR, 0.483; 95% CI, 0.357-0.654) and overall survival (adjusted HR, 0.373; 95% CI, 0.265-0.526). CONCLUSION: This study provides real-world evidence supporting the survival benefit of earlier immunochemotherapy administration in patients with ES-SCLC. These findings add to the growing body of knowledge on the clinical relevance of circadian timing in cancer treatment. CLINICAL TRIAL REGISTRATION: Not applicable.