Overall survival according to time-of-day of combined immuno-chemotherapy for advanced non-small cell lung cancer: a bicentric bicontinental study

作者：Zhe Huang, Abdoulaye Karaboué, Liang Zeng, Adrien Lecoeuvre, Lemeng Zhang, Xiaomei Li, Haoyue Qin, Gabrielle Danino, Feng Yang, Marie-Sara Malin, Li Deng, Marte Rigal, Hong Liu, Xiang Chen, Qinqin Xu, Lamiae Grimaldi, T. Collon, Jing Wang, René Adam, Nong Yang, Boris Duchemann, Yongchang Zhang, Françis Lévi · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.105607 · 被引用次数：46 · 研究领域：Circadian rhythm and melatonin、Dietary Effects on Health、Cancer, Stress, Anesthesia, and Immune Response

BACKGROUND: Circadian rhythms regulate immune cell activity, influencing responses to vaccines, and immune checkpoint inhibitors (ICIs). Early time-of-day administration (ToDA) of singe-agent ICIs has been associated with improved overall survival (OS) in patients with metastatic "immunotherapy sensitive" cancers. However, the impact of ToDA on OS in patients receiving combination therapy with ICIs and chemotherapy for advanced non-small cell lung cancer (NSCLC) remains unclear. METHODS: This retrospective study included patients from oncology units in Paris, France (Cohort 1) and Hunan, China (Cohort 2) who received first-line immuno-chemotherapy for stage IIIC or IV NSCLC between January 2018 and October 2023. The primary outcome was OS. The median ToDA of the initial four ICI infusions was computed for each patient. Hazard ratio (HR) for death or progression were determined using cut-off times ranging from 10:30 to 13:00. Kaplan Meier and Cox models were used to estimate OS and progression-free survival (PFS) adjusting for main patient characteristics. FINDINGS: The study included 713 patients (Cohort 1, n = 165; Cohort 2, n = 548). Pembrolizumab was the most common ICI (51%), which was used with either pemetrexed-carboplatin/cisplatin (49%) or paclitaxel-carboplatin (51%). The optimal ToDA cut-off was 11:30, with patients receiving immuno-chemotherapy before 11:30 showing significantly improved OS (33.0 months [95% CI, 27.5-41.0] vs 19.5 months [18.0-22.5]; p < 0.0001). M...