Retrospective study of overall survival according to time-of-day of combined immuno-chemotherapy for advanced non-small cell lung cancer

Prof. Francis Lévi

Circadian rhythms regulate immune cell activity, possibly influencing responses to immune checkpoint inhibitors (ICIs). A retrospective study in Paris, France (n=165) and Hunan, China (n=548) evaluated time-of-day administration (ToDA) of standard first-line ICIs plus chemotherapy for stage IIIC or IV non-small cell lung cancer. The primary outcome was overall survival (OS). The median ToDa of the initial four infusion was computed for each patients. The optimal ToDA cut-off was 11:30, with patients receiving immuno-chemotherapy before 11:30 showing significantly improved OS compared with patients receiving immuno-chemotherapy after 11:30 (median 33.0 months versus 19.5 months; p<0.0001). Multivariable analysis confirmed that earlier ToDA was associated with better OS (aHR 0.47; 95% CI 0.37-0.60). Comparable results were seen in the separate cohorts. The authors conclude that this bicontinental retrospective study suggests that morning administration of standard first-line immuno-chemotherapy was associated with improved OS. Randomized trials are required to validate this finding and inform recommendations for clinical practice.