{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:46:50Z","timestamp":1791395210513,"version":"4.3.3"},"reference-count":62,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To conduct a comprehensive network meta-analyses (NMA) to include latest advances in BTC therapy to guide clinical practice.<\/jats:p>\n <\/jats:sec>\n \n Data Sources<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Study Selection<\/jats:title>\n Phase 2 to 3 RCTs of unresectable, locally advanced, or metastatic BTC reporting progression-free survival (PFS) or overall survival (OS) were eligible.<\/jats:p>\n <\/jats:sec>\n \n Data Extraction and Synthesis<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Primary outcomes were PFS and OS; secondary outcomes included objective response rate (ORR) and grade 3 to 4 adverse events.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and relevance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.6849","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T15:30:26Z","timestamp":1776267026000},"page":"e266849","source":"Crossref","is-referenced-by-count":2,"title":["First-Line Chemotherapy Regimens for Unresectable Locally Advanced or Metastatic Biliary Tract Cancer"],"prefix":"10.1001","volume":"9","author":[{"given":"Abdulaziz","family":"Elemosho","sequence":"first","affiliation":[{"name":"Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex B.","family":"Blair","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Ohio State University Wexner Medical 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