ArticleCancers2022
Time-Dependent Efficacy of Checkpoint Inhibitor Nivolumab: Results from a Pilot Study in Patients with Metastatic Non-Small-Cell Lung Cancer.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 83 citations in OpenAlex.
- Time-of-Day Immunotherapy Administration and Outcomes in Advanced Cancers: A Systematic Review and Meta-Analysis.JAMA network open · 2026Pooled it
- Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis.ESMO open · 2024Pooled it
- Morning versus afternoon administration of immune checkpoint inhibitors in metastatic non-small-cell lung cancer.Journal for immunotherapy of cancer · 2026Trial
- Circadian timing of first-line chemoimmunotherapy is associated with survival in extensive-stage small cell lung cancer.Oncoimmunology · 2026Article
- The impact of gut microbiota and metabolite-driven immune cell spatiotemporal dynamics on tumors.Gut microbes · 2026Review
- The Immune Checkpoint Inhibitors Journey: From Early Promise to Lasting Impact.Journal of immunotherapy and precision oncology · 2026Review
- Role of the circadian rhythm in squamous cell carcinoma: From molecular mechanism to therapy (Review).Molecular medicine reports · 2026Review
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- 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
- Chronotherapy in Oncology: Aligning Cancer Treatment with Biological Time.Journal of personalized medicine · 2026Review
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Timing of immune checkpoint inhibitors infusion and prognosis in recurrent/metastatic nasopharyngeal carcinoma: a single-center, retrospective study.Cancer immunology, immunotherapy : CII · 2026Article
- Real-world evidence for the impact of circadian clock on the benefit from immune checkpoint inhibitors in solid tumors.BMC cancer · 2026Article
- The circadian gene Dec2 promotes pancreatic cancer progression and dormancy through immune evasion.Developmental cell · 2026Article
- Circadian rhythms and lung cancer biology and immunotherapy: Emerging opportunities and challenges.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Circadian-immune-related gene signature for lung squamous cell carcinoma: machine learning and multi-omics analysis.Translational cancer research · 2026Article
- 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
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
hypothesisPrior experimental and human studies have demonstrated the circadian organization of immune cells' proliferation, trafficking, and antigen recognition and destruction. Nivolumab targets T(CD8) cells, the functions, and trafficking of which are regulated by circadian clocks, hence suggesting possible daily changes in nivolumab's efficacy. Worse progression-free survival (PFS), and overall survival (OS) were reported for malignant melanoma patients receiving more than 20% of their immune checkpoint inhibitor infusions after 16:30 as compared to earlier in the day.
methodsConsecutive metastatic non-small-cell cancer (NSCLC) patients received nivolumab (240 mg iv q 2 weeks) at a daily time that was 'randomly' allocated for each course on a logistical basis by the day-hospital coordinators. The median time of all nivolumab administrations was computed for each patient. The study population was split into two timing groups based upon the median value of the median treatment times of all patients. CTCAE-toxicity rates, iRECIST-tumor responses, PFS and OS were computed according to nivolumab timing. PFS and OS curves were compared and hazard ratios (HR) were computed for all major categories of characteristics. Multivariable and sensitivity analyses were also performed.
resultsThe study accrued 95 stage-IV NSCLC patients (PS 0-1, 96%), aged 41-83 years. The majority of nivolumab administrations occurred between 9:27 and 12:54 for 48 patients ('morning' group) and between 12:55 and 17:14 for the other 47 ('afternoon' group). Median PFS (95% CL) was 11.3 months (5.5-17.1) for the 'morning' group and 3.1 months (1.5-4.6) for the 'afternoon' one (
conclusionsNivolumab was nearly four times as effective following 'morning' as compared to 'afternoon' dosing in this cohort of NSCLC patients. Prospective timing-studies are needed to minimize the risk of resistance and to maximize the benefits from immune checkpoint inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.