FDA approve tucatinib for advanced unresectable or metastatic HER2-positive breast cancer

Seattle Genetics have announced the U.S. Food and Drug Administration (FDA) have granted approval for tucatinib in combination with trastuzumab and capecitabine for adult patients with advanced unresectable or metastatic HER2-positive breast cancer. This approval includes patients with brain metastases, and those who have received one or more prior anti-HER2-based regimens in the metastatic setting.

HER2-positive breast cancer is usually more aggressive compared with HER2-negative breast cancer,1 and up to 50% of patients with metastatic HER-2 positive breast cancer develop brain metastases.2

Tucatinib is an oral tyrosine kinase inhibitor (TKI) of HER-2.3,4 The efficacy of tucatinib in combination with trastuzumab and capecitabine was evaluated in the HER2CLIMB study (NCT02614794) – a randomized (2:1), double-blind, placebo-controlled involving 612 patients, of which almost half had the presence or history of brain metastases. The full results of the study were published in December 2019 in The New England Journal of Medicine,5 and reported that patients who received the three-drug combination had a 46% reduction in the risk of cancer progression or death compared with patients who received trastuzumab and capecitabine alone (HR=0.54 [95% CI: 0.42, 0.71]; p<0.00001). In patients with brain metastases the addition of tucatinib reduced the risk of cancer progression or death by 52% compared with trastuzumab and capecitabine alone (HR=0.48 [95% CI: 0.34, 0.69]; p<0.00001).

Following the approval from the FDA,6 Eric P. Winer, MD, Chief of the Division of Breast Oncology from the Susan F. Smith Center for Women’s Cancers at Dana-Farber commented that:

“With highly significant and clinically important results for overall and progression-free survival, the addition of tucatinib to trastuzumab and capecitabine has the potential to become a standard of care for people with HER2-positive metastatic breast cancer after having received one or more previous anti-HER2 therapies in the metastatic setting’

“Cancer spreads to the brain in up to half of patients with HER2-positive metastatic breast cancer; and this approval is based on a unique clinical trial that included patients with active brain metastases, either untreated or progressing. Tucatinib is well tolerated by patients and is a valuable addition to the agents we have for HER2-positive metastatic breast cancer.”


  1. Breast Cancer HER2 Status. American Cancer Society website. Available from: https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html (Last accessed 22/04/2020).  
  2. Olson EM, Najita JS, Sohl J, et al. Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era. Breast. 2013;22:525-531.
  3. TUKYSA [package insert]. Bothell, WA: Seattle Genetics, Inc.
  4. Kulukian A, Lee P, Taylor J, et al. Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor Models. Mol Cancer Ther. 2020;19:976-987.
  5. Murthy RL, Loi S, Okines A, et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2020;382:597-609.
  6. Seattle Genetics Announces U.S. FDA Approval of TUKYSA™ (tucatinib) for People with Advanced Unresectable or Metastatic HER2-Positive Breast Cancer. Available from: https://investor.seattlegenetics.com/press-releases/news-details/2020/Seattle-Genetics-Announces-US-FDA-Approval-of-TUKYSA-tucatinib-for-People-with-Advanced-Unresectable-or-Metastatic-HER2-Positive-Breast-Cancer/default.aspx (Last accessed 22/04/2020).