Immunotherapy Time of Infusion Impacts Survival in Head and Neck Cancer: A Propensity Score Matched Analysis

Abstract

AbstractThe adaptive immune response is physiologically regulated by the circadian rhythm. Data in lung and melanoma malignancies suggests immunotherapy infusions earlier in the day may be associated with improved response; however, the optimal time of administration for patients with HNSCC is not known. We aimed to evaluate the association of immunotherapy infusion time with overall survival (OS) and progression free survival (PFS) in patients with HNSCC in an Institutional Review Board-approved, retrospective cohort study. 113 patients met study inclusion criteria and 98 patients were included in a propensity score-matched cohort. In the full unmatched cohort (N=113), each additional 20% of infusions received after 1500h conferred an OS hazard ratio (HR) of 1.35 (95% C.I.1.2-1.6; p-value=0.0003) and a PFS HR of 1.34 (95% C.I.1.2-1.6; p-value <0.0001). A propensity score-matched analysis of patients who did or did not receive ≥ 20% of infusions after 1500h showed that those who were administered ≥20% of infusions after 1500h trended towards a shorter OS (HR=1.35; p-value=0.26) and a shorter PFS (HR=1.57, 95% C.I. 1.02-2.42, p-value=0.04). Each additional 20% of infusions received after 1500h remained robust in the matched cohort multivariable analysis and was associated with shorter OS (adjusted HR=1.4 (95% C.I.1.2-1.8), p-value<0.001). Patients with advanced HNSCC who received more of their infusions in the afternoon were associated with shorter OS and PFS and scheduling immunotherapy infusions earlier in the day may be warranted.Conflict of Interest StatementDr. Wirth reports receiving advisory board fees from Ayala Pharmaceuticals, Blueprint Medicines, Cue Biopharma, Cullinan Oncology, Genentech USA, Loxo Oncology, Merck, NewLink Genetics, Novartis, and Rakuten Medical, consulting fees and advisory board fees from Bayer HealthCare Pharmaceuticals and Eisai, advisory board fees and fees for serving on a steering committee from Eli Lilly, and fees for serving on a data and safety monitoring board from Iovance Biotherapeutics. Dr. Faden has received research funding from Bristol Myers Squibb and Foundation Medicine, holds equity in Illumina and receives consulting fees from Noetic and Focus on Boston. The remaining authors have no conflicts to report.Research HighlightsImmunotherapy early in the day may result in improved response rates in HNSCC, consistent with data in other solid malignancies.