Effect of immune checkpoint inhibitor administration timing on survival outcomes in advanced biliary tract cancers: A single-center propensity score matching analysis.

Abstract

e16186 Background: Circadian rhythms in the immune system and anti-tumor immune responses have not received adequate attention in terms of their impact on cancer immunotherapy. Recent advances in immune checkpoint inhibitors (ICIs) have marked a significant breakthrough in the treatment of advanced biliary tract cancer (BTC), but not all patients benefit from this therapy. Our study aimed to investigate whether the timing of ICI administration affects the treatment outcomes in BTC patients. Methods: We included patients with advanced BTC patients at West China Hospital of Sichuan University who received at least two ICI treatments from October 2019 to May 2023, with follow-up until December 2023. The primary outcome was overall survival (OS), with secondary outcomes including progression-free survival (PFS), objective response rate (ORR), and adverse event incidence. Propensity score matching (1:2 ratio, nearest-neighbor caliper width of 0.1) and COX regression were used to analyze the relationship between the proportion of ICI administrations after 16:30 and both OS and PFS, while the Chi-square test was used to compare the ORR and adverse event rates between groups. Results: A total of 207 patients were eligible for analysis. Before matching, 37 patients had more than 20% of their ICI administrations after 16:30, and 170 had less than 20%. After matching, 34 patients receiving more than 20% of ICIs after 16:30 were compared with 65 who did not. The former group showed significantly shorter OS (median 10 months [95%CI: 8-14 months] vs. 17 months [95%CI: 12-20 months], HR = 2.067 [95%CI: 1.226-3.485, P = 0.00645]) and PFS (median 5 months [95%CI: 4-7 months] vs. 9 months [95%CI: 8-12 months], HR = 2.093 [95%CI: 1.315-3.331, P = 0.00183]), with these results remaining robust after multivariate Cox regression analysis. No significant difference in ORR (χ^2 = 2.287, p = 0.131) was observed. Safety analysis showed no difference in the incidence of adverse events, including Grade 3/4 adverse events, immune-related adverse events, and medication discontinuation due to adverse events (all p > 0.050). Sensitivity analyses in patients receiving at least three ICI treatments revealed similar results. Conclusions: The timing of ICI administration influences the efficacy of immunotherapy in advanced biliary cancer, with administrations before 16:30 associated with better survival outcomes. Further research with larger sample sizes and prospective studies is needed to validate these findings.