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.