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

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EBioMedicine Pub Date : 2025-03-01 Epub Date: 2025-02-20 DOI:10.1016/j.ebiom.2025.105607

Zhe Huang, Abdoulaye Karaboué, Liang Zeng, Adrien Lecoeuvre, Lemeng Zhang, Xiao-Mei Li, Haoyue Qin, Gabrielle Danino, Feng Yang, Marie-Sara Malin, Li Deng, Marte Rigal, Hong Liu, Xiang Chen, Qinqin Xu, Lamiae Grimaldi, Thierry Collon, Jing Wang, René Adam, Nong Yang, Boris Duchemann, Yongchang Zhang, Francis Lévi

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Abstract

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). Multivariable analysis confirmed that earlier ToDA was associated with better OS (adjusted HR = 0.47 [95% CI, 0.37-0.60]). ToDA significantly impacted OS in each cohort and for PFS and response rates in each cohort and the pooled data.

Interpretation: This sizeable bi-continental study provided real-world evidence that morning administration of standard first-line immuno-chemotherapy was associated with improved clinical outcomes compared to afternoon dosing in patients with NSCLC. Randomised trials are required to validate this finding and inform recommendations for clinical practice.

Funding: National Natural Science Foundation of China (82222048, 82003206, 82173338, and 82102747).

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根据时间对晚期非小细胞肺癌联合免疫化疗的总生存率：一项双中心双洲研究。

背景：昼夜节律调节免疫细胞活性，影响对疫苗和免疫检查点抑制剂（ICIs）的反应。在转移性“免疫治疗敏感”癌症患者中，单药ICIs的早期给药（ToDA）与改善总生存率（OS）相关。然而，ToDA对晚期非小细胞肺癌（NSCLC）患者接受ICIs和化疗联合治疗的OS的影响尚不清楚。方法：这项回顾性研究包括来自法国巴黎（队列1）和中国湖南（队列2）的肿瘤科患者，他们在2018年1月至2023年10月期间接受了IIIC或IV期非小细胞肺癌的一线免疫化疗。主要结果是OS。计算每位患者初始四次ICI输注的中位ToDA。死亡或进展的危险比（HR）使用截止时间从10:30到13:00确定。Kaplan Meier和Cox模型用于估计经主要患者特征调整后的OS和无进展生存期（PFS）。结果：该研究纳入713例患者(队列1，n = 165；队列2，n = 548)。派姆单抗是最常见的ICI(51%)，它与培美曲塞-卡铂/顺铂（49%）或紫杉醇-卡铂（51%）一起使用。最佳ToDA截止时间为11:30，在11:30之前接受免疫化疗的患者OS明显改善(33.0个月[95% CI， 27.5-41.0] vs 19.5个月[18.0-22.5]；p解释：这项规模庞大的双大陆研究提供了真实的证据，证明与下午给药相比，上午给药的标准一线免疫化疗与改善非小细胞肺癌患者的临床结果相关。需要随机试验来验证这一发现，并为临床实践提供建议。国家自然科学基金项目（82222048,82003206,82173338,82102747）。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.