Retrospective cohort study uncovers no survival benefit from first-infusion timing in renal cell carcinoma, suggesting late-day cumulative associations require further study.
Key Points
To evaluate the association between the time-of-day of immune checkpoint inhibitor infusion and overall survival in patients with renal cell carcinoma.
Retrospective cohort analysis of 117 patients receiving first- or second-line immune checkpoint inhibitor therapy at Dana-Farber Cancer Institute (median follow-up 33 months).
Assessed overall survival across multiple cutoffs for the initial infusion (C1D1: <12 PM vs ≥12 PM; <3 PM vs ≥3 PM; <12 PM vs 12–4 PM vs >4 PM) and a cumulative definition (≥25% vs <25% of all infusions after 4:30 PM).
Used Cox proportional hazards models adjusted for age, sex, season, tumor mutational burden, and line of therapy, with a 3-month landmark analysis to address immortal time bias.
Initial infusion (C1D1) timing showed no significant association with overall survival at <12 PM vs ≥12 PM (HR 0.77, 95% CI 0.47–1.27, p = 0.31), <3 PM vs ≥3 PM (HR 0.98, 95% CI 0.59–1.62, p = 0.93), or across three time intervals.
Cumulative late-day exposure (≥25% infusions after 4:30 PM, n=15 vs <25%, n=102) was associated with significantly worse overall survival (HR 1.93, 95% CI 1.01–3.67, p = 0.046).
The survival disadvantage for cumulative late infusions persisted in a 3-month landmark analysis (HR 2.14, 95% CI 1.11–4.12, p = 0.023).