by Dr. C.H. Weaver M.D. 10/2019
Tucatinib in combination with trastuzumab and Xeloda (capecitabine) improves outcomes for women with locally advanced unresectable or metastatic HER2-positive breast cancer compared to treatment with trastuzumab and Xeloda alone.
“There is significant unmet medical need following treatment with trastuzumab, pertuzumab and T-DM1 in patients with metastatic HER2-positive breast cancer,” said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics, We plan to submit a New Drug Application (NDA) to the FDA in the first quarter of 2020, with the goal of bringing a much-needed new medicine to patients.”
About HER2-Positive Breast Cancer
Patients with HER2-positive breast cancer have cancer with high levels of a protein called human epidermal growth factor receptor 2 (HER2) which promotes the aggressive spread of cancer cells. Between 15 and 20 percent of individuals with breast cancer are HER2-positive. There are several approved treatments for HER2-positive breast cancer but currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2-positive metastatic breast cancer after progression on T-DM1. (1,2,3)
Tucatinib is a tyrosine kinase inhibitor drug that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR is associated with significant side effects including skin rash and diarrhea. HER2 is a growth factor receptor that is over expressed in multiple cancers, including breast, colorectal and gastric cancers. HER2 mediates cell growth, differentiation, and survival. Tucatinib has been granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases.
The HER2CLIMB clinical trial compared tucatinib in combination with trastuzumab and Xeloda to treatment with trastuzumab and Xeloda alone in patients with locally advanced or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab and T-DM1 in 612 patients.
The addition of tucatinib to trastuzumab and Xeloda improved patient outcomes: Compared to trastuzumab and Xeloda the addition of tucatinib:
- Resulted in a 46 percent reduction in the risk of disease progression or death.
- Improved overall survival, with a 34 percent reduction in the risk of death compared to trastuzumab and Xeloda alone.
- Resulted in a 52 percent reduction in the risk of disease progression or death in patients with brain metastases compared to trastuzumab and Xeloda alone.
Tucatinib in combination with trastuzumab and Xeloda was generally well tolerated with a manageable safety profile. The most frequent side effects were diarrhea, palmar-plantar erythrodysaesthesia syndrome (PPE), nausea, fatigue, and vomiting.
- Verma S, Miles D, Gianni L, et al. (2012). Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. New England Journal of Medicine 367(19): 1783-91.
- Meyer CE, Forster J, Lindquist D, et al. (2006). Lapatinib plus Xeloda for HER2-Positive Advanced Breast Cancer. New England Journal of Medicine 355(26): 2733-43.
- Blackwell KL, Burstein HJ, Storniolo AM, et al. (2012). Overall Survival Benefit With Lapatinib in Combination With Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Final Results From the EGF104900 Study. Journal of Clinical Oncology 30(21): 2585-92.