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.
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.
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.