Biliary cancer: gateway to comprehensive molecular profiling

Area of Science:

• Oncology
• Genetics
• Gastroenterology

Background:

• Cholangiocarcinoma (CCA) is a rare cancer with poor prognosis.
• Advanced stages and post-surgical relapse are common.
• Standard chemotherapy (cisplatin/gemcitabine) and second-line FOLFOX offer limited benefit.

Purpose of the Study:

• To review the efficacy of targeted therapies in cholangiocarcinoma.
• To highlight genetic aberrations driving treatment selection.
• To inform clinical trial participation for improved patient outcomes.

Main Methods:

• Review of clinical trial data for targeted therapies in CCA.
• Analysis of response rates, disease stability, progression-free survival (PFS), and overall survival (OS).
• Focus on agents targeting FGFR2 fusions, IDH1 mutations, and BRAF mutations.

Main Results:

• FGFR2 fusion inhibitors: 20.7–35.5% response rates, 5.7–6.9 months median PFS, 12.5–21.1 months median OS.
• Ivosidenib (IDH1/2 mutation): 2% response rate, 2.7 months median PFS, 10.8 months median OS.
• Dabrafenib/trametinib (BRAF mutation): 51% response rate, 9 months median PFS, 14 months median OS.

Conclusions:

• Targeted therapies demonstrate significant efficacy in genetically defined cholangiocarcinoma subtypes.
• Agents targeting FGFR2 fusions show particularly promising results.
• Clinical trial enrollment is crucial for patients with advanced or relapsed cholangiocarcinoma.