A randomized, double-blind study of PF-05280014 (a potential biosimilar) vs trastuzumab, both given with docetaxel (D) and carboplatin (C), as neoadjuvant treatment for operable human epidermal growth factor receptor 2-positive (HER2+) breast cancer

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.

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Pertuzumab: Unprecedented benefit in human epidermal growth factor receptor 2-positive breast cancer

Asian Journal of Oncology ◽

10.4103/2454-6798.173299 ◽

2015 ◽

Vol 01 (02) ◽

pp. 084-091

Author(s):

Amit Rauthan ◽

Palanki Dattatreya ◽

Manish Singhal ◽

Ram Prabu ◽

Siddharth Naik ◽

...

Keyword(s):

Breast Cancer ◽

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

Human Epidermal Growth Factor ◽

Her2 Breast Cancer ◽

Epidermal Growth ◽

Positive Breast Cancer

ABSTRACTHuman epidermal growth factor receptor 2 (HER2)-positive breast cancer is a more aggressive subtype of breast cancer and targeting the HER2 receptor has proven effective in improving the prognosis of these patients. Pertuzumab, a recombinant humanized monoclonal antibody and the first in a class of HER2 dimerization inhibitors approved for treating HER2+ breast cancer. It blocks ligand-dependent heterodimerization and ligand-independent homodimerization of HER2 with other HER members. When used in combination with trastuzumab and taxane, pertuzumab complements the action of trastuzumab and results in a comprehensive blockade of HER2 signaling pathway. This review article traces the development of pertuzumab from concept to its current use in HER2+ breast cancer treatment. A search of Medical Literature Published since 2007 was performed in PubMed using the keywords “pertuzumab,” “HER2+ breast cancer,” “HER2 targeted therapy,” “metastatic breast cancer,” and in search engines for ongoing trials with pertuzumab and incidence of cancer and breast cancer in India. A total of 35 publications and abstracts from the American Society of Clinical Oncology were selected for this review. Pertuzumab is approved in combination with trastuzumab and docetaxel for the treatment of patients with HER2+ metastatic BC, who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. The dual HER2 blockade of pertuzumab and trastuzumab is now accepted worldwide as a standard of care by various guidelines.

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