Efficacy and safety of targeted therapy and immune checkpoint inhibitors in patients with advanced or metastatic biliary tract cancer: a meta-analysis of and sequential analysis of trials.

[OBJECTIVE] This study aimed to comprehensively evaluate the efficacy and safety of targeted therapy and immune checkpoint inhibitors (ICIs) in patients with advanced or metastatic biliary tract cancer (BTC).

[METHODS] A comprehensive literature search was conducted in PubMed, Embase, and Web of Science databases through October 2024. The outcomes assessed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse events (AEs). Hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CIs) were used to quantify each outcome.

[RESULTS] Fifteen studies met the inclusion criteria. Pooled analyses revealed that targeted and immune therapy significantly improved OS and PFS compared to control. Subgroup analyses identified significant OS benefits with PD-L1 inhibitors, IDH1 inhibitors, and PD-1 inhibitors. In contrast, anti-EGFR agents, MET inhibitors, and anti-VEGF agents did not significantly prolong OS. PFS was improved with IDH1 inhibitors, PD-L1 inhibitors, and PD-1 inhibitors, while anti-VEGF agents showed no significant PFS benefit. Targeted and immune therapy significantly improved ORR and DCR, as confirmed by trial sequential analysis (TSA). Incidences of all-grade, serious, and grade 3/4 AEs were comparable between the targeted and immune therapy and control groups. Meta-regression analysis revealed no significant influence of sample size, treatment duration, or publication year on OS and PFS outcomes.

[CONCLUSION] This meta-analysis demonstrates that targeted and immune therapy significantly improves survival outcomes and overall response in patients with advanced or metastatic BTC. Considering the potential limitations, further large-scale studies are warranted to validate these findings.