A HER2-directed Therapy for Colorectal Cancer 

The FDA approved tucatinib for certain patients with unresectable or metastatic colorectal cancer. 

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to tucatinib (Tukysa) in combination with trastuzumab for the treatment of certain patients with unresectable or metastatic HER2-positive colorectal cancer that has progressed following chemotherapy. 

Tucatinib is a small molecule inhibitor of the HER2 receptor. HER2 overexpression leads to tumor cell proliferation, invasion, and metastasis and is found in approximately 3 to 5 percent of metastatic colorectal cancers.  

The approval was based on results from the phase II, open-label, multicenter MOUNTAINEER trial, conducted in patients with HER2-positive, unresectable or metastatic colorectal cancer whose tumors did not carry alterations in the RAS gene and whose disease progressed after treatment with the chemotherapy drugs fluoropyrimidine, oxaliplatin, and irinotecan and an anti-vascular endothelial growth factor targeted therapy. To be included in this study, patients whose tumors had DNA repair deficiencies had to have received prior immune checkpoint inhibitor treatment. 

Study participants received tucatinib with trastuzumab, a HER2-targeted monoclonal antibody, until disease progression or unacceptable toxicity. The overall response rate was 38 percent, and the median duration of response was 12.4 months. 

Colorectal cancer is the second most common cause of cancer death in the U.S. According to federal statistics, it was estimated that more than 151,000 people would be diagnosed with colorectal cancer, and more than 52,000 people would die of the disease in the U.S. in 2022. 

The FDA rendered its decision on January 19, 2023. Accelerated approval means that continued approval may be contingent upon a confirmatory trial.