Timing of the infusion of nivolumab for patients with recurrent or metastatic squamous cell carcinoma of the esophagus influences its efficacy

Background The immune system is affected by the circadian rhythm. The objective of this study was to clarify whether time-of-day patterns (early or late in the daytime) of the infusion of nivolumab and whether its duration affect treatment efficacy in metastatic or recurrent esophageal squamous cell carcinoma (R/M-ESCC). Methods The data of 62 consecutive patients with R/M-ESCC treated with nivolumab between February 2017 and May 2022 were retrospectively reviewed. The infusion of nivolumab before 13:00 was set as ‘early in the day’, and that after 13:00 was set as ‘late in the day’. The treatment efficacy was compared between early and late groups by 3 criteria (first infusion, during the first 3 months, and all treatment courses). Results The overall survival, progression-free survival, and response rate of patients received the first dose in the early group were significantly superior to those of patients in the late group. The progression-free survival and response rate of patients who received the majority of nivolumab infusions before 13:00 during the first 3 months were significantly superior to those who received it after 13:00, with the exception of overall survival. There were no significant differences in the overall survival, progression-free survival, and response rate between patients who received the majority of nivolumab infusions before 13:00 of all treatment courses and those who received it after 13:00. Conclusion The timing of the infusion of nivolumab may affect treatment efficacy in R/M-ESCC.