Tukysa (tucatinib) – HER2 Inhibitor for Treatment of Breast Cancer
by Dr. C.H. Weaver M.D. updated 4/2020
Tukysa (tucatinib) in combination with Herceptin (trastuzumab) and Xeloda (capecitabine) improves outcomes for women with locally advanced unresectable or metastatic HER2-positive breast cancer compared to treatment with Herceptin and Xeloda alone leading to Food and Drug Administration on April 17, 2020. (1-5)
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)
About Tukysa (tucatinib)
Tukysa 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. Tukysa has been granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases.
The HER2CLIMB clinical trial compared Tukysa in combination with Herceptin and Xeloda to treatment with Herceptin and Xeloda alone in patients with locally advanced or metastatic HER2-positive breast cancer who were previously treated with Herceptin, pertuzumab and T-DM1 in 612 patients.
Trial results were updated at the December 2019 San Antonio Breast Cancer Symposia. The addition of Tukysa to Herceptin and Xeloda significantly improved the outcomes of women with advanced HER2 + breast cancer including women with brain metastases. Compared to treatment with Herceptin and Xeloda, the addition of Tukysa
- Resulted in a 46% reduction in the risk of disease progression or death.
- Improved overall survival, with a 34% reduction in the risk of death compared to Herceptin and Xeloda. Estimated survival at two years was 45% with the addition of Tukysa compared to 27% for Herceptin + Xeloda. Median survival duration was improved to 22 months compared to 17 months.
- Delayed cancer progression; 33% of Tukysa treated patients survived one year without cancer progression compared to only 12% for Herceptin + Xeloda.
- Resulted in a 52 percent reduction in the risk of disease progression or death in patients with brain metastases compared to Herceptin and Xeloda.
Tukysa in combination with Herceptin 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. Tukysa has the potential to improve the treatment of advanced HER2 + breast cancer and is undergoing evaluation in women with early stage disease.
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- 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.
- USA Food and Drug Administration. FDA Approves First New Drug Under International Collaboration, A Treatment Option for Patients with HER2-Positive Metastatic Breast Cancer. Updated April 17, 2020. www.fda.gov/news-events/press-announcements/fda-approves-first-new-drug-under-international-collaboration-treatment-option-patients-her2 Accessed April 17, 2020.