Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis

Jan 17, 2024ESMO open

Time of day for immunotherapy infusions may affect survival in advanced cancer patients

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Abstract

Pooled analyses of 13 studies involving 1663 patients indicate that early administration of immune checkpoint inhibitors is associated with significantly longer overall survival and progression-free survival.

Patients receiving immune checkpoint inhibitors (ICIs) in the early time of day had a hazard ratio of 0.50 for overall survival compared to those receiving ICIs later.
The hazard ratio for progression-free survival was 0.51 for early ToD groups versus late ToD groups.
The studies included various cancers, with non-small-cell lung cancer being the most common (47%).
The timing of ICI administration may relate to circadian rhythms affecting immune cell functions and responses.

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BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for numerous malignancies. Emerging evidence suggests that the time of day (ToD) of ICI administration could impact the outcomes of patients with cancer. The consistency of ToD effects on ICI efficacy awaits initial evaluation.

MATERIALS AND METHODS: This meta-analysis integrates progression-free survival (PFS) and overall survival (OS) data from studies with a defined 'cut-off' ToD. Hazard ratios (HRs) [95% confidence interval (CI)] of an earlier progression or death according to 'early' or 'late' ToD of ICIs were collected from each report and pooled.

RESULTS: Thirteen studies involved 1663 patients (Eastern Cooperative Oncology Group performance status 0-1, 83%; males/females, 67%/33%) with non-small-cell lung cancer (47%), renal cell carcinoma (24%), melanoma (20%), urothelial cancer (5%), or esophageal carcinoma (4%). Most patients received anti-programmed cell death protein 1 or anti-programmed death-ligand 1 (98%), and a small proportion also received anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) (18%). ToD cut-offs were 13:00 or 14:00 (i.e. ICI median infusion time), for six studies, and 16:00 or 16:30 (i.e. reported threshold for weaker vaccination responses) for seven studies. Pooled analyses revealed that the early ToD groups had longer OS (HR 0.50, 95% CI 0.42-0.58; P < 0.00001) and PFS (HR 0.51, 95% CI 0.42-0.61; P < 0.00001) compared with the late ToD groups.

CONCLUSIONS: Patients with selected metastatic cancers seemed to largely benefit from early ToD ICI infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking. Prospective randomized trials are needed to establish recommendations for optimal circadian timing of ICI-based cancer therapies.

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Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis

Abstract

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