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Review

Preclinical Characteristics of the Irreversible Pan-HER Kinase Inhibitor Neratinib Compared with Lapatinib: Implications for the Treatment of HER2-Positive and HER2-Mutated Breast Cancer

1
National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, 9 Dublin, Ireland
2
Bioinformatics Institute, A*STAR (Agency for Science, Technology and Research), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore
3
Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore
4
School of Biological Sciences, Nanyang Technological University, 50 Nanyang Drive, Singapore 637551, Singapore
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Puma Biotechnology, Inc., 10880 Wilshire Blvd., Suite 2150, Los Angeles, CA 90024, USA
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Department of Medical Oncology, St Vincent’s University Hospital, 4 Dublin, Ireland
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(6), 737; https://doi.org/10.3390/cancers11060737
Received: 29 March 2019 / Revised: 16 May 2019 / Accepted: 17 May 2019 / Published: 28 May 2019
An estimated 15–20% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2/ERBB2/neu). Two small-molecule tyrosine kinase inhibitors (TKIs), lapatinib and neratinib, have been approved for the treatment of HER2-positive (HER2+) breast cancer. Lapatinib, a reversible epidermal growth factor receptor (EGFR/ERBB1/HER1) and HER2 TKI, is used for the treatment of advanced HER2+ breast cancer in combination with capecitabine, in combination with trastuzumab in patients with hormone receptor-negative metastatic breast cancer, and in combination with an aromatase inhibitor for the first-line treatment of HER2+ breast cancer. Neratinib, a next-generation, irreversible pan-HER TKI, is used in the US for extended adjuvant treatment of adult patients with early-stage HER2+ breast cancer following 1 year of trastuzumab. In Europe, neratinib is used in the extended adjuvant treatment of adult patients with early-stage hormone receptor-positive HER2+ breast cancer who are less than 1 year from the completion of prior adjuvant trastuzumab-based therapy. Preclinical studies have shown that these agents have distinct properties that may impact their clinical activity. This review describes the preclinical characterization of lapatinib and neratinib, with a focus on the differences between these two agents that may have implications for patient management. View Full-Text
Keywords: tyrosine kinase inhibitors; lapatinib; neratinib; HER2; breast cancer tyrosine kinase inhibitors; lapatinib; neratinib; HER2; breast cancer
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MDPI and ACS Style

Collins, D.M.; Conlon, N.T.; Kannan, S.; Verma, C.S.; Eli, L.D.; Lalani, A.S.; Crown, J. Preclinical Characteristics of the Irreversible Pan-HER Kinase Inhibitor Neratinib Compared with Lapatinib: Implications for the Treatment of HER2-Positive and HER2-Mutated Breast Cancer. Cancers 2019, 11, 737. https://doi.org/10.3390/cancers11060737

AMA Style

Collins DM, Conlon NT, Kannan S, Verma CS, Eli LD, Lalani AS, Crown J. Preclinical Characteristics of the Irreversible Pan-HER Kinase Inhibitor Neratinib Compared with Lapatinib: Implications for the Treatment of HER2-Positive and HER2-Mutated Breast Cancer. Cancers. 2019; 11(6):737. https://doi.org/10.3390/cancers11060737

Chicago/Turabian Style

Collins, Denis M., Neil T. Conlon, Srinivasaraghavan Kannan, Chandra S. Verma, Lisa D. Eli, Alshad S. Lalani, and John Crown. 2019. "Preclinical Characteristics of the Irreversible Pan-HER Kinase Inhibitor Neratinib Compared with Lapatinib: Implications for the Treatment of HER2-Positive and HER2-Mutated Breast Cancer" Cancers 11, no. 6: 737. https://doi.org/10.3390/cancers11060737

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