Dr. Marks on the Role of TKIs in HER2-Positive Breast Cancer

Douglas K. Marks, MD
Published: Wednesday, Sep 04, 2019



Douglas K. Marks, MD, clinical instructor, Department of Medicine, Perlmutter Cancer Center, NYU Langone Health, discusses the role of TKIs in HER2-positive breast cancer.

TKIs have taken a backseat to HER2-directed antibodies over the past few years. This is due, in part, to the fact that lapatinib (Tykerb) and neratinib (Nerlynx) were found to be inferior to other agents that were developed around the same time, like pertuzumab (Perjeta) and ado-trastuzumab emtansine (T-DM1; Kadcyla). However, these agents have re-emerged after demonstrating impressive central nervous system activity (CNS), says Marks.

For example, the irreversible pan-ErbB inhibitor pyrotinib demonstrated potent CNS activity in a phase II study published in the Journal of Clinical Oncology. In the trial, combining the agent with capecitabine led to a 64% reduction in the risk of disease progression or death compared with lapatinib plus capecitabine in Chinese patients with relapsed or metastatic HER2-positive breast cancer. Tucatinib is another TKI that has shown promise and is currently being evaluated in the ongoing phase II HER2CLIMB trial.
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Douglas K. Marks, MD, clinical instructor, Department of Medicine, Perlmutter Cancer Center, NYU Langone Health, discusses the role of TKIs in HER2-positive breast cancer.

TKIs have taken a backseat to HER2-directed antibodies over the past few years. This is due, in part, to the fact that lapatinib (Tykerb) and neratinib (Nerlynx) were found to be inferior to other agents that were developed around the same time, like pertuzumab (Perjeta) and ado-trastuzumab emtansine (T-DM1; Kadcyla). However, these agents have re-emerged after demonstrating impressive central nervous system activity (CNS), says Marks.

For example, the irreversible pan-ErbB inhibitor pyrotinib demonstrated potent CNS activity in a phase II study published in the Journal of Clinical Oncology. In the trial, combining the agent with capecitabine led to a 64% reduction in the risk of disease progression or death compared with lapatinib plus capecitabine in Chinese patients with relapsed or metastatic HER2-positive breast cancer. Tucatinib is another TKI that has shown promise and is currently being evaluated in the ongoing phase II HER2CLIMB trial.



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