RECEIVING immune checkpoint inhibitor therapy earlier in the day may be associated with substantially longer survival amongst patients with advanced cancer, according to new research.
The large UK cohort study found that patients who received most of their immune checkpoint inhibitor (ICI) infusions earlier in the day had a median overall survival of 21.4 months, compared with 13.1 months amongst those treated later.
ICIs have transformed treatment across multiple cancer types by enhancing the immune system’s ability to recognise and target cancer cells. However, treatment response can vary considerably between patients.
Growing evidence suggests that circadian rhythms may influence the effectiveness of immunotherapy. Immune functions, including immune cell proliferation, migration, antigen recognition, and cytokine circulation, fluctuate throughout the day, raising the possibility that the timing of treatment could affect outcomes.
Researchers at The Christie NHS Foundation Trust, Manchester, UK, therefore investigated the association between ICI administration time and overall survival in patients with advanced cancer.
The retrospective study included 2,631 adults receiving ICIs between January 2018 and December 2023. Participants had advanced or metastatic lung cancer, melanoma, renal cell carcinoma, head and neck cancer, or urothelial cancer.
The median treatment time was 12:49. Patients were classified according to whether at least half of their ICI infusions occurred after this time. Those with 50% or more of their treatments after 12:49 formed the late group, while the remaining patients formed the early group.
After a median follow-up of 32 months, substantial differences in overall survival were observed between the two groups.
Median overall survival was 21.4 months amongst patients in the early group, compared with 13.1 months amongst those in the late group. One-year overall survival was also higher with earlier treatment, at 65.7% compared with 52.5%.
After adjusting for factors including age, sex, performance status, cancer type, and treatment, patients in the late-treatment group had a 48% higher risk of death compared with those treated earlier.
Researchers also used a time-dependent statistical model to address immortal time bias, a potential limitation of previous retrospective studies examining treatment timing. In this analysis, later ICI administration remained associated with a 30% higher risk of death.
However, the association was not significant for every individual treatment regimen. Earlier administration appeared particularly beneficial with combination immunotherapy, while no association was observed amongst regimens combining ICIs with chemotherapy.
The findings add to growing evidence that the body’s circadian rhythms could influence the effectiveness of immunotherapy. Previous research has shown that immune cells involved in anticancer responses fluctuate in both number and activity throughout the day.
If confirmed, altering ICI administration times could represent a relatively simple intervention requiring no change in treatment dose or drug selection.
However, the authors emphasised several limitations. As a retrospective, single-centre study, the research cannot establish that earlier administration directly improves survival. Important tumour-specific prognostic factors were unavailable, and other differences between patients receiving earlier and later appointments could have influenced the results.
For example, patients who are frailer or more symptomatic may require additional clinical assessment before treatment, potentially resulting in later infusions.
The researchers conclude, however, that their findings provide further evidence supporting earlier ICI administration, but a large prospective randomised trial is needed to determine whether treatment timing itself improves survival.
Reference
Bosetti T et al. Overall survival according to timing of immune checkpoint inhibitors administration in patients with advanced cancer: results from a large single-centre cohort analysis. Br J Cancer (2026).
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