PD-1/PD-L1 inhibitors combined with chemotherapy as first-line treatment for advanced biliary tract cancer: a systematic review and meta-analysis
In brief
PD-1 inhibitors plus chemo cut death risk by 20% in advanced biliary cancer
A meta-analysis of five randomized trials (about 2,000 patients) found that adding PD-1/PD-L1 blockade to first-line chemotherapy reduced overall mortality by roughly one-fifth and improved progression-free survival and response rates, without raising severe toxicity. Retrospective data showed even larger benefits, but prospective confirmation in broader populations is still needed.
- Journal
- Frontiers in medicine (Q1)
- Published
- 3 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Hongye Geng, Chengyuan Lu, Shuling Wang, Lijuan Tian
- PMID
- 42755819
- DOI
- 10.3389/fmed.2026.1916331
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (top studies of the week, 20 September 2026): systematic review of PD‑1/PD‑L1 plus chemo in advanced biliary tract
Abstract
OBJECTIVE: To systematically evaluate the efficacy and safety of PD-1/PD-L1 inhibitors plus chemotherapy as first-line treatment for advanced biliary tract cancer (BTC). METHODS: PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases were searched for RCTs and retrospective studies. Meta-analysis was performed using R 4.6.1 software with the meta (v8.5-0) and metafor (v5.0-1) packages. The full R code and datasets are provided in the supplementary material to ensure reproducibility. RESULTS: Part I included 5 RCTs with 2,000 patients; of these, only 2 phase III RCTs (TOPAZ-1 and KEYNOTE-966, n = 1,754) reported OS and PFS data, while all 5 RCTs reported ORR and DCR data; Part II included 6 retrospective studies with 1,253 patients. RCT meta-analysis showed: OS was significantly improved (HR = 0.80, 95% CI: 0.72-0.89, p < 0.001); PFS was also significantly improved (HR = 0.81, 95% CI: 0.71-0.93, p = 0.002); ORR was significantly higher (RR = 1.38, 95% CI: 1.02-1.87, p = 0.037). Retrospective study meta-analysis showed: PFS was significantly superior (HR = 0.52, 95% CI: 0.43-0.63, p < 0.001); OS was significantly prolonged (HR = 0.61, 95% CI: 0.42-0.87, p = 0.017); ORR (RR = 1.97, 95% CI: 1.43-2.71, p = 0.004) and DCR (RR = 1.26, 95% CI: 1.09-1.45, p = 0.014) were also significantly higher. Neither part showed significantly increased severe adverse events. CONCLUSION: PD-1/PD-L1 inhibitors plus chemotherapy significantly improves survival outcomes and objective response rate in advanced BTC without increasing severe adverse event risk. SYSTEMATIC REVIEW REGISTRATION: PROSPERO. Unique Identifier: CRD420261401842 URL: https://www.crd.york.ac.uk/prospero/display_record.php?
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.