by Dr. C.H. Weaver M.D. updated 9/2022
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. The US Food and Drug Administration approved Tukysa on April 17, 2020.1-5 Importantly The Tukysa regimen is also very effective for treating brain metastases.6-8
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.
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.
The initial trial results were released 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
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- 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.
An update was released at the 2021 ASCO Annual Meeting showing that Tukysa maintained and even improved overall survival. The survival benefit with Tukysa was maintained at 30 months from initiation of treatment. The median survival duration was 24.7 months with Tukysa versus 19.2 months. Tukysa also reduced the risk of disease progression or death by 40% in patients with brain metastases.9
Tukysa Prolongs Survival in Breast Cancer Characterized by Brain Metastases
Nearly half of the patients with advanced HER2-positive breast cancer enrolled in the HER2CLIMB trial had disease that had metastasized to the brain. Forty percent of these patients treated with Tukysa survived without cancer progression one year from treatment compared with 0%. The one-year overall survival rate was 70% for those treated with Tukysa versus 46.7% for those receiving placebo.6-8
Dr. Nancy U. Lin, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, author of the study, noted that “Tukysa is the first tyrosine kinase inhibitor precision cancer medicine to demonstrate prolonged survival in a controlled trial evaluating patients with HER2-positive metastatic breast cancer with brain metastases. Dr Lin concluded that “these results together with the HER2CLIMB primary analysis demonstrate that the Tukysa triplet and an active regimen for both intracranial and extracranial disease in patients with HER2-positive metastatic breast cancer.”
Importnantly 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.
- 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.
- Lin NU, Murthy RK, Anders CK, et al, Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB). Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 1005.
- Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-Positive metastatic breast cancer. N Engl J Med. 2020;382:597-609.
- Tucatinib (Tukysa) [package insert]. Bothell, WA: Seattle Genetics, Inc.; 2020.
- Curigliano G, Mueller V, Borges V, et al. Updated results of tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with or without brain metastases, J Clin Oncol. 2021;39(suppl 15; abstr 1043). doi:10.1200/JCO.2021.39.15_suppl.1043