Timing of immune checkpoint inhibitors infusion and prognosis in recurrent/metastatic nasopharyngeal carcinoma: a single-center, retrospective study

BACKGROUND: The timing of immunotherapy administration has been linked to variations in clinical outcome across multiple cancers, but its effect on clinical outcome in nasopharyngeal carcinoma (NPC) remains unstudied. METHODS: In this single-center retrospective cohort study, patients with recurrent/metastatic (R/M) NPC who received first-line anti-PD-1-based immunochemotherapy (June 2019-December 2024) were included. The primary endpoint was progression-free survival (PFS), and overall survival (OS) was the secondary endpoint. Data regarding the time of day of administration (ToDA) during the initial four cycles were collected for each patient. Survival was estimated by the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox models were adjusted for prespecified covariates. Propensity score matching (PSM) was performed between patients from different ToDA groups. The ToDA cutoff was derived from the data without a prespecified hypothesis, using a data-driven approach. RESULTS: Among the 334 screened patients, 312 met the eligibility criteria. The median follow-up was 24.9 months. The median PFS was 25.0 months, and the mOS was not reached. A data-driven optimal ToDA cutoff of 12:00 was identified. Patients who received immunotherapy after 12:00 had significantly longer PFS (31.2 vs. 18.3 months, p = 0.006) and OS (both not reached, p = 0.011). After PSM at a 1:2 ratio, PFS (36.1 vs. 18.3 months, p = 0.003) and OS (both not reached, p = 0.018) were still significantly improved in patients who received immunotherapy after 12:00. Multivariate analysis demonstrated that a ToDA after 12:00 was independently correlated with improved PFS (HR=0.63; 95% CI: 0.43-0.92; p = 0.017) and OS (HR=0.48; 95% CI: 0.27-0.84; p = 0.010). CONCLUSIONS: These hypothesis-generating findings suggest that, in R/M NPC patients treated with first-line immunochemotherapy, afternoon administration during the initial four cycles may be associated with improved PFS and OS. However, because the ToDA threshold was selected post hoc, the results should be interpreted with caution. Randomized clinical trials are warranted to validate these findings.