timing of immune checkpoint inhibitor administration and overall survival in advanced cancer

Timing of immune checkpoint inhibitor administration and overall survival in advanced cancer

Overview

• retrospective cohort study evaluating whether time-of-day of immune checkpoint inhibitor (ICI) infusion affects overall survival (OS) in patients with advanced solid tumours
• cohort included 2,631 patients treated at a tertiary cancer centre between January 2018 and December 2023
• median follow-up was 32–38 months; median patient age was 68.2 years (61% male)
• cancer types: non-small cell lung cancer (45%), melanoma (23%), renal cell carcinoma (18%), head and neck cancer (9%), urothelial carcinoma (5%)

Study groupings and definition of timing

• overall median infusion time across all treatment cycles was 12:49 pm
• early group: patients receiving <50% of their total ICI cycles after 12:49 pm
• late group: patients receiving >=50% of their total ICI cycles after 12:49 pm

Primary findings

• median overall survival (OS):
  • early group: 21.4 months (95% CI 19.8 to 24.5)
  • late group: 13.1 months (95% CI 11.8 to 14.4)
• hazard ratio (HR) for OS (late vs. early):
  • standard Cox multivariate analysis: HR 1.48 (95% CI 1.33 to 1.63), indicating shorter survival in the late group
  • time-dependent Cox model (adjusting for immortal time bias): HR 1.30 (95% CI 1.16 to 1.44)
• subgroup variations by regimen:
  • significant survival association retained for monotherapy ICIs and ICIs combined with tyrosine kinase inhibitors (TKIs)
  • no significant survival difference observed in patients receiving combined ICI plus chemotherapy regimens

Proposed biological mechanism

• hypothesized to be driven by circadian rhythmicity of the host immune system, influencing T-cell activation, antigen presentation, and immune cell trafficking in response to checkpoint blockade

Clinical application and limitations

• key study strengths:
  • large real-world UK cohort; use of time-dependent models to account for potential immortal time bias
• confounding factors and unadjusted variables:
  • observational design cannot fully exclude confounding; frailer, more symptomatic patients, or those requiring hospital transport may experience treatment delays or routine afternoon scheduling
• current clinical recommendation:
  • findings are hypothesis-generating and should not immediately alter routine UK scheduling pathways until prospective, randomised clinical trials confirm the benefit

Reference:

1. Bosetti T, Kennedy OJ, Califano R, Waddell T, Metcalf R, Kreft S, Lee R, Lorigan P. 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