First-Line Chemotherapy Regimens for Unresectable Locally Advanced or Metastatic Biliary Tract Cancer: A Systematic Review and Bayesian Network Meta-Analysis
A partir d'une revue systématique de la littérature publiée entre 2000 et 2025 (33 essais, 7 303 patients), cette méta-analyse évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité des stratégies thérapeutiques de première ligne à base de chimiothérapie pour prendre en charge les patients atteints d'un cancer des voies biliaires non résécable de stade localement avancé ou métastatique
Importance : Biliary tract cancers (BTCs) are aggressive malignant neoplasms with a dismal prognosis. Recent advancements, including immunotherapy and targeted therapies, have expanded therapeutic options, yet head-to-head comparisons between regimens remain limited.
Objective : To conduct a comprehensive network meta-analyses (NMA) to include latest advances in BTC therapy to guide clinical practice.
Data Sources : PubMed, Embase, and Cochrane Central were searched for randomized clinical trials (RCT) from 2000 to 2024, with manual updates through August 2025 and conference abstracts and ClinicalTrials.gov screened.
Study Selection : Phase 2 to 3 RCTs of unresectable, locally advanced, or metastatic BTC reporting progression-free survival (PFS) or overall survival (OS) were eligible.
Data Extraction and Synthesis : The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline was followed. Two reviewers independently extracted data, resolving discrepancies with a third. Data were pooled with a fixed-effect model.
Main Outcomes and Measures : Primary outcomes were PFS and OS; secondary outcomes included objective response rate (ORR) and grade 3 to 4 adverse events.
Results : This systematic review and bayesian NMA synthesized data from 33 RCTs involving 7303 patients (median [IQR] age, 64 [63-65] years; 3704 [51.5%] male). Compared with gemcitabine plus cisplatin (GC), GC plus sintilimab plus anlotinib (hazard ratio [HR], 0.47; 95% CI, 0.28-0.80), GC plus S-1 (HR, 0.75; 95% CI, 0.59-0.97), and GC plus durvalumab (HR, 0.80; 95% CI, 0.66-0.97) were associated with highest PFS benefits. Capecitabine plus oxaliplatin (HR, 0.64; 95% CI, 0.44-0.92), GC plus durvalumab (HR, 0.71; 95% CI, 0.61-0.84), and gemcitabine plus oxaliplatin (GO) (HR, 0.78; 95% CI, 0.63-0.96) were associated with improved OS. ORR was highest with GC plus S-1 (odds ratio [OR], 4.13; 95% CI, 2.20-7.70), GC plus cediranib (OR, 3.20; 95% CI, 1.40-7.20), and GC plus durvalumab (OR, 1.60; 95% CI, 1.10-2.28) compared with GC. Toxicity profiles showed no significant hematological differences between regimens, but nonhematological risks varied. Overall, GC plus durvalumab, GC plus S-1, GO plus panitumumab, and GO plus cetuximab showed the greatest consistency in the surface under the cumulative ranking curve value for PFS, OS, ORR, and safety.
Conclusions and relevance : This NMA establishes GC plus durvalumab and GC plus S-1 as potential leading first-line options for advanced BTC due to a consistent clear benefit in PFS, OS, ORR, and safety. This study also establishes that GC remains among the top regimens, as most other therapy lacked a clear superior benefit or were associated with worse PFS or OS compared with GC.
JAMA Network Open , article en libre accès, 2026