Abstract
BACKGROUND AND AIMS: A single immune checkpoint inhibitor (ICI) regimen has limited value in treating advanced bile tract cancer (BTC); therefore, ICI combination therapy is often applied. This meta-analysis aimed to evaluate the effectiveness and safety of ICI combination therapy for advanced BTC. METHODS: The study protocol was registered on PROSPERO (CRD42023452422). Data on the median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and grade ≥3 adverse events (AEs) reported in relevant studies were pooled and analyzed to determine the efficacy and safety of ICI combination therapy. RESULTS: In total, 15 studies with 665 patients were included in this meta-analysis. The overall ORR and DCR were 34.6% and 77.6%, respectively. The overall median PFS and OS were 6.06 months [95% confidence interval (CI): 4.91-7.21] and 12.11 months (95% CI: 10.66-13.55), respectively. Patients receiving ICI combination therapy in addition to other therapies had a considerably prolonged median PFS and OS (z=9.69, p<0.001 and z=16.17, p<0.001). Patients treated as first-line treatment had a substantially longer median PFS and OS compared to patients treated as non-first-line treatment (z=11.19, p<0.001 and z=49.17, p<0.001). The overall pooled grade ≥3 AEs rate was 38.2% (95% CI: 0.268-0.497) and was not influenced by whether ICI therapy was combined with other treatments or not or the treatment line. CONCLUSION: Advanced BTC patients may benefit from ICI combination treatment without additional AEs. However, concurrent chemotherapy or radiotherapy is still needed to achieve better outcomes. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42023452422.