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First-Line Chemotherapy Regimens for Unresectable Locally Advanced or Metastatic Biliary Tract Cancer: A Systematic

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Network meta-analysis shows gemcitabine plus cisplatin plus durvalumab (GC) and GC plus S-1 offer superior progression-free survival (PFS) and overall survival (OS) for biliary tract cancers (BTC). These regimens are potential leading first-line options for advanced BTC.

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Area of Science:

  • Oncology
  • Medical research
  • Clinical trials

Background:

  • Biliary tract cancers (BTCs) are aggressive and have a poor prognosis.
  • Recent therapeutic advancements offer new options, but direct comparisons are limited.

Purpose of the Study:

  • To conduct a network meta-analysis (NMA) of recent biliary tract cancer therapies.
  • To guide clinical practice by comparing treatment efficacy and safety.

Main Methods:

  • Searched PubMed, Embase, and Cochrane Central for Phase 2-3 randomized clinical trials (RCTs) from 2000-2024.
  • Synthesized data from 33 RCTs involving 7303 patients using a Bayesian NMA.
  • Evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events.

Main Results:

  • Gemcitabine plus cisplatin plus durvalumab (GC) demonstrated the highest PFS benefits (HR 0.47) and improved OS (HR 0.71).
  • GC plus S-1 showed significant PFS (HR 0.75) and highest ORR (OR 4.13).
  • Toxicity profiles were comparable, with GC plus durvalumab and GC plus S-1 showing consistent benefits across outcomes.

Conclusions:

  • GC plus durvalumab and GC plus S-1 are potential leading first-line treatments for advanced BTC.
  • These regimens offer clear benefits in PFS, OS, ORR, and safety.
  • Gemcitabine plus cisplatin (GC) remains a strong backbone regimen for BTC treatment.