Purpose of review: This manuscript aims at providing an update and overview on the role of Human epidermal growth factor receptor 2 (HER2) testing and HER2-directed therapies in digestive tumors.
Recent findings: Phase 3 trial data demonstrating a survival benefit of HER2-targeting treatments are limited to gastric cancer. However, HER2 positivity is also found in 5-6% of colorectal, 7% of pancreatic, and 16% of extrahepatic biliary cancers. Although phase 2 trial data support the use of the combination of trastuzumab and lapatinib with chemotherapy in HER2-positive colorectal cancer, the patient's benefit from targeted treatment of HER2-positive biliary or pancreatic neoplasms is currently unclear, and further clinical trials are necessary.
Summary: With the exception of gastric cancer, there are currently no defined guidelines for HER2 testing in other digestive tumors. Various HER2-targeting therapies, which are standard of care in HER2-positive breast cancer, failed in HER2-positive gastric cancers. Thus, the predictive value of HER2 overexpression depends on the tumor type, and results of breast cancer trials cannot a priori be extrapolated to digestive cancers. Next-generation sequencing panel diagnostics may furthermore identify targetable activating mutations in gastric, extrahepatic biliary, and colorectal cancer, particularly if traditional testing (immunohistochemistry/in-situ hybridization) is negative. However, their clinical relevance needs to be determined.