Chemoimmunotherapy in Advanced Biliary Tract Cancers: A Meta-Analysis of Clinical Outcomes

Background/Objectives: Biliary tract cancers (BTCs), encompassing tumors of the bile ducts, gallbladder, or ampulla of Vater, are notoriously hard to manage, especially when surgery is off the table and standard chemotherapy provides only modest benefits. While emerging treatments such as immune checkpoint inhibitors have shown promise, mixed clinical trial results and varied study endpoints have left their true impact unclear. This concise review consolidates current evidence on combining chemotherapy with immunotherapy to clarify whether these regimens can significantly improve outcomes and steer more effective treatment strategies for BTCs. Methods: A comprehensive literature search was conducted across PubMed, Embase, Web of Science, and ClinicalTrials.gov for randomized controlled trials (RCTs) and prospective comparative studies published from January 2010 to December 2024. Fixed-effect meta-analyses (inverse-variance method) were used as the primary approach, with random-effects models (REML) performed as sensitivity analyses to confirm robustness were performed to calculate pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS). Leave-one-out sensitivity analyses and Egger's tests assessed result stability and publication bias. The review was conducted in accordance with PRISMA 2020 guidelines and registered in OSF. Results: Two RCTs (n = 1754; chemoimmunotherapy n = 874, chemotherapy n = 880) were included in the quantitative meta-analysis. Compared to chemotherapy alone, chemoimmunotherapy significantly reduced the risk of death by 20% (OS, HR = 0.80; 95% CI 0.72-0.89; I² = 0%) and the risk of disease progression or death by 19% (PFS, HR = 0.81; 95% CI 0.73-0.90; I² = 33.5%). Leave-one-out sensitivity analyses confirmed result stability. Egger's tests showed no significant publication bias (OS p = 0.30; PFS p = 0.40). Two additional studies (IMbrave 151 and Monge 2022) lacking comparative survival data were qualitatively assessed. Conclusions: Chemoimmunotherapy significantly improves OS and PFS compared with chemotherapy alone in advanced BTC, with consistent findings across included trials. These results support the incorporation of chemoimmunotherapy as a first-line therapeutic strategy. Future research should prioritize biomarker-driven patient selection, evaluation of long-term clinical outcomes, and integration of targeted therapies with chemoimmunotherapy.