Open AccessTreating Advanced Unresectable or Metastatic HER2-Positive Breast Cancer: A Spotlight on Tucatinib
Author(s) -
Lara Ulrich,
Alicia Okines
Publication year - 2021
Publication title -
breast cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.19
H-Index - 27
ISSN - 1179-1314
DOI - 10.2147/bctt.s268451
Subject(s) - medicine , trastuzumab , neratinib , capecitabine , metastatic breast cancer , oncology , taxane , pertuzumab , trastuzumab emtansine , breast cancer , tyrosine kinase inhibitor , pharmacology , cancer , colorectal cancer
The management of HER2 positive breast cancer has been transformed by the development of targeted therapies. Dual blockade with the monoclonal antibodies, trastuzumab and pertuzumab, added to first-line taxane chemotherapy and second-line therapy with the antibody-drug conjugate, T-DM1, are internationally agreed standards of care for advanced HER2 positive breast cancer, where available. However, until recently, options for patients for third-line therapy and beyond were of modest efficacy or limited by toxicity. In 2019, the results of trials of two exciting new agents for this space were presented. A third-generation HER2 tyrosine kinase inhibitor, tucatinib, combines the efficacy of the second-generation drug, neratinib, with a more manageable toxicity profile and has become a new standard of care after T-DM1, in combination with capecitabine and trastuzumab. The antibody-drug conjugate, trastuzumab deruxtecan, demonstrated remarkable efficacy in heavily pre-treated patients and received accelerated approval in the United States, whilst confirmatory Phase 3 trials are completed. This review will discuss the available data for the post-T-DM1 setting, focusing on tyrosine kinase inhibitors including tucatinib.