ArticleEBioMedicine2025
Overall survival according to time-of-day of combined immuno-chemotherapy for advanced non-small cell lung cancer: a bicentric bicontinental study.
Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
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Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Time-of-Day Immunotherapy Administration and Outcomes in Advanced Cancers: A Systematic Review and Meta-Analysis.JAMA network open · 2026Pooled it
- PD-1/PD-L1 inhibitors plus chemotherapy versus chemotherapy alone for Chinese patients with advanced non-small-cell lung cancer: an updated meta-analysis based on phase 3 randomized controlled trials.World journal of surgical oncology · 2025Pooled it
- Time-of-day immunochemotherapy in non-small cell lung cancer: a randomized phase 3 trial.Nature medicine · 2026Trial
- Circadian timing of first-line chemoimmunotherapy is associated with survival in extensive-stage small cell lung cancer.Oncoimmunology · 2026Article
- Overall survival according to timing of immune checkpoint inhibitors administration in patients with advanced cancer: results from a large single-centre cohort analysis.British journal of cancer · 2026Article
- Unlocking the clock: a systematic review and meta-analysis on optimizing immune checkpoint inhibitor timing for advanced solid tumors.British journal of cancer · 2026Article
- Translational modelling challenges receptor‑occupancy‑based dosing of PD‑1 inhibitors like pembrolizumab.British journal of cancer · 2026Article
- Cancer Chemoimmunotherapy: Time Will Tell.Cancer immunology research · 2026Article
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Circadian-guided oncolytic virotherapy for glioblastoma.Journal of neurovirology · 2026Review
- Timing of immune checkpoint inhibitors infusion and prognosis in recurrent/metastatic nasopharyngeal carcinoma: a single-center, retrospective study.Cancer immunology, immunotherapy : CII · 2026Article
- Circadian rhythms and lung cancer biology and immunotherapy: Emerging opportunities and challenges.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Circadian engineering of in vivo CAR T cell therapy for precision oncology.NPJ precision oncology · 2026Review
- Article
- Time-of-day of first checkpoint inhibitor dose influences clinical outcomes and immune responses in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- Serum exosomal miR-192-5p as a novel predictive biomarker for immunochemotherapy response in advanced non-small cell lung cancer.BMC cancer · 2026Article
- Obesity and Cancer: From Systemic Metabolic Reprogramming to Immunotherapy Paradox.Metabolites · 2026Review
- Optimizing oral contraceptive timing: Daytime intake reduces doses and enhances efficacy.PLoS computational biology · 2026Article
- Impact of time-of-day on immune checkpoint inhibitor therapy in cancer patients: an up-to-date clinical review.Frontiers in immunology · 2026Review
- Timing of immune checkpoint inhibitor infusion predicts survival in advanced esophageal squamous cell carcinoma: A retrospective cohort study.Therapeutic advances in medical oncology · 2026Article
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Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCircadian 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.
methodsThis 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.
findingsThe 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.
interpretationThis 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.
fundingNational Natural Science Foundation of China (82222048, 82003206, 82173338, and 82102747).
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