HER2/neu-directed therapy for biliary tract cancer

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Biliary cancers are aggressive, often diagnosed late, with poor outcomes.
• A subset of biliary cancers exhibits HER2/neu amplification or mutation.
• HER2/neu-targeted therapy is effective in other cancers, but its role in biliary cancers is unclear.

Purpose of the Study:

• To evaluate the efficacy of HER2/neu-directed therapy in advanced biliary cancers.
• To assess response rates and clinical outcomes in patients with HER2/neu aberrations.

Main Methods:

• Retrospective review of advanced gallbladder cancer and cholangiocarcinoma cases.
• Patients received HER2/neu-directed therapy (trastuzumab, lapatinib, pertuzumab) between 2007-2014.
• Clinical data and imaging studies were analyzed.

Main Results:

• Nine gallbladder cancer patients received HER2/neu-directed therapy; eight had HER2/neu amplification/overexpression and showed stability or response.
• One gallbladder cancer patient with HER2/neu mutation had a mixed response.
• Five cholangiocarcinoma patients with HER2/neu mutations showed no radiological response to HER2/neu-directed therapy.

Conclusions:

• HER2/neu blockade is a promising strategy for gallbladder cancer with gene amplification.
• Further multi-center studies are needed to explore HER2/neu-targeted therapy in biliary cancers.
• Response appears specific to HER2/neu amplification in gallbladder cancer, not mutations in cholangiocarcinoma.