Update for: New developments in systemic therapy for advanced biliary tract cancer

Area of Science:

• Oncology
• Gastroenterology
• Pharmacology

Background:

• Biliary tract cancers (BTC), including gallbladder, ampullary, and intrahepatic cholangiocarcinoma, are frequently diagnosed at advanced stages.
• Traditional treatment for advanced BTC relies on cytotoxic chemotherapy regimens.

Purpose of the Study:

• To review recent advancements in systemic therapy for advanced biliary tract cancers.
• To highlight updated first-line and second-line treatment strategies and emerging targeted therapies.

Main Methods:

• Review of current clinical practice guidelines and recent clinical trial data for advanced BTC treatment.
• Analysis of efficacy data for immunotherapies, standard chemotherapy, and targeted agents.

Main Results:

• First-line therapy: Gemcitabine plus cisplatin combined with immune checkpoint inhibitors (durvalumab or pembrolizumab) demonstrates improved overall survival compared to gemcitabine plus cisplatin alone.
• Second-line therapy: Fluorouracil, folinic acid, and oxaliplatin remain a standard second-line option post-gemcitabine-based regimens.
• Targeted therapies: Agents targeting FGFR2 fusions, IDH1/2, KRAS, BRAF mutations, and HER2 overexpression show promise in later-line settings.

Conclusions:

• Immune checkpoint inhibitor combinations represent a new standard for first-line treatment of advanced BTC, improving patient outcomes.
• Targeted therapies offer novel treatment avenues for specific molecular alterations in advanced BTC, expanding therapeutic options beyond chemotherapy.