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N. U. Lin, V. Dieras, D. Paul, et al., “A Phase II Study of Lapatinib for Brain Metastases in Subjects with ErbB2-Positive Breast Cancer Following Trastuzumab-Based Systemic Therapy and Cranial Radiotherapy,” Proceedings of American Society of Clinical Oncology, Vol. 27, 2007, Abstr 1012.

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• TITLE: Lapatinib, a TKI Dual Inhibitor of Her1 and Her2 Receptors: Review of the Literature

  AUTHORS: Vito Lorusso, Ilaria Marech, Marianna Giampaglia, Antonio Gnoni, Andrea Tinelli

  KEYWORDS: Lapatinib; Tyverb®; HER2; Breast Cancer; TKI

  JOURNAL NAME: Journal of Cancer Therapy, Vol.3 No.6, December 18, 2012

  ABSTRACT: Lapatinib ditosylate (Tyverb?) is a potent and selective oral dual receptor tyrosine kinase inhibitor (TKI), preventing autophosphorylation of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2) intracellular domain. This interference blocks the Ras/Raf MAPKs and PI3K/Akt pathways, that lead to uncontrolled cellular proliferation and survival. After the demonstration of its effectiveness and safety in HER2-overexpressed breast cancer, in 2007 the US Food and Drug Administration (FDA) approved this molecule in combination with capecitabine, in patients with locally advanced or metastatic disease, that progressed after previous treatment with anthracyclines, taxanes and trastuzumab. In 2010, Lapatinib received approval for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer in combination with letrozole. The most common adverse events (AE) are: anorexia, insomnia, diarrhea and skin rash and mild cardiovascular toxicity. This paper reviews the most important studies on Lapatinib in advanced breast cancer. However, promising results were recently reported on this drug, also in adjuvant setting and in combination with other target drugs, which warrant further investigation for the future.