Circadian timing of first-line chemoimmunotherapy is associated with survival in extensive-stage small cell lung cancer.

Growing evidence suggests that circadian timing influences the efficacy of immune checkpoint inhibitors across multiple malignancies. However, evidence in extensive-stage small cell lung cancer (ES-SCLC) remains limited to a single East Asian cohort, and independent validation in other populations is lacking. We conducted a retrospective single-center cohort study of 107 patients with ES-SCLC treated with first-line platinum-etoposide plus atezolizumab or durvalumab. The time of day of administration (ToDA) was defined as the median start time of the first four immunotherapy infusions, and patients were categorized according to the cohort median ToDA. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The cohort median ToDA was 11:54. Patients treated before the median ToDA had significantly longer median PFS (9.07 vs. 7.23 months, p = 0.002) and OS (21.17 vs. 11.43 months, p = 0.002) than those treated later. In multivariable Cox regression analysis, later administration remained independently associated with shorter PFS (adjusted HR 1.63, 95% CI 1.03-2.58; p = 0.038) and OS (adjusted HR 1.65, 95% CI 1.00-2.71; p = 0.049), whereas objective response rates, treatment-related toxicity, and immune-related adverse events were comparable between groups. Morning administration of first-line chemoimmunotherapy was associated with significantly longer survival without increased toxicity in patients with ES-SCLC. These findings support growing evidence that circadian timing may influence immune checkpoint inhibitor efficacy and warrant prospective evaluation of treatment timing as a readily modifiable strategy to optimize immunotherapy delivery.