The efficacy and role of tucatinib/tucatinib

Tucatinib/Tucatinib is an oral small molecule inhibitor of human epidermal growth factor receptor 2 (HER2). By inhibiting tyrosine kinases, tucatinib exerts anti-tumor activity and reduces the size of HER-2-positive breast cancer tumors. In clinical trials, the tucatinib and trastuzumab regimen demonstrated enhanced activity both in vivo and in vitro compared with administration alone.

Tucatinib has been shown to extend the survival time of patients with advanced or metastatic HER2-positive breast cancer without making the disease worse. In an ongoing major study, patients treated with tucatinib lived an average of 7.8 months without disease progression, and about 41% of patients had some response to the treatment, with an average lifespan of 22 months. In another study, the combination of tucatinib and trastuzumab may become a new standard treatment option. At a median duration of follow-up of 20.7 months, by blinded independent central review, 86 patients with metastatic colorectal cancer treated with tucatinib and trastuzumab had a confirmed objective response rate of 38.1% and a disease control rate of 71.4%. The median duration of response was 12.4 months, the median progression-free survival was 8.2 months, and the median overall survival was 24.1 months.

Mutations in the HER-2 gene are seen in some types of breast cancer. Tucatinib inhibits the tyrosine kinase of the HER-2 gene. 1 Mutations in the tyrosine kinase in the HER-2 gene lead to a cascade of increased cell signaling and proliferation, leading to malignancy. 6 In vitro study results show that tucatinib inhibits the phosphorylation of HER-2 and HER-3, leading to downstream changes in MAPK and AKT signaling and cell proliferation. Cells expressing HER-2 have anti-tumor activity. In vivo, tucatinib may inhibit HER-2-expressing tumors via the same mechanism.