Lapatinib and breast cancer: current indications and outlook for the future

Abstract

Lapatinib is an oral dual erbB 1/2 tyrosine kinase inhibitor that inhibits human EGF receptor 2 (HER2) and blocks the EGF receptor. Studies have shown that in patients with metastatic HER2-positive breast cancer that is resistant to trastuzumab, the addition of lapatinib to capecitabine improves progression-free survival and appears to lengthen overall survival. Furthermore, lapatinib has been studied in patients with involvement of the CNS and has been associated with stable disease and some responses. Its combination with letrozole provided an improvement in progression-free survival compared with single-agent letrozole in women with hormone receptor-positive, HER2-positive metastatic breast cancer. More recently, data suggested that the combination of lapatinib with trastuzumab significantly improves overall survival in women with metastatic breast cancer compared with single-agent lapatinib. Current indications in the USA for the use of lapatinib are for the treatment of metastatic HER2-positive breast cancer, both in combination with capecitabine in patients who have received taxane, anthracycline and traztuzumab, and in combination with letrozole for postmenopausal patients with hormone receptor- and HER2-overexpressing breast cancer. Common side effects of lapatinib include diarrhea and rash. Studies to date have found a less than 2% risk for cardiotoxicity, although most cardiac events that occurred during the studies were not attributed to lapatinib. It is important to consider that most of the patients in existing studies had already been treated with trastuzumab with no significant cardiotoxicity; therefore, future studies will show how trastuzumab-naive patients tolerate lapatinib. Ongoing research is evaluating the role of lapatinib in the adjuvant setting as a single agent or in combination with trastuzumab.

Synergistic antitumor activity of lapatinib and retinoids on a novel subtype of breast cancer with coamplification of ERBB2 and RARA

“…þ patients used to have a poor prognosis until the advent of targeted therapy (Baselga, 2006;Baselga and Swain, 2009), which relies on trastuzumab (Esteva et al;Mariani et al, 2009) and lapatinib (Moreira and Kaklamani, 2010). In spite of this progress, not all patients in this group benefit from trastuzumab-based therapies (Hudis, 2007;Esteva et al, 2010).…”

Mesenchymal stem cells and carcinoma-associated fibroblasts sensitize breast cancer cells in 3D cultures to kinase inhibitors

“…In breast cancer, depending on the subtype (22)(23)(24), Her2, EGFR and/or FGFR are the major RTKs that are responsible for the activation of these pathways (25,26). Inhibition of the RTKs are among the routinely used strategies to treat patients with breast cancer (27). Alternatively, drugs may be used that directly target components of the Ras/Raf/MEK/ERK1/2 and the PI3K/AKT/ mTOR pathways (28)(29)(30).…”

I Diretriz Brasileira de Cardio-Oncologia da Sociedade Brasileira de Cardiologia

“…Lapatinibe: o lapatinibe é uma quinazolina oral que tem com o alvo EGFR e ERBB2 180 , É utilizado no tratamento do câncer metastático de mama. Entretanto, diferentemente do trastuzumabe, a cardiotoxicidade desse fármaco é evento raro, sendo descrita redução assintomática da FEVE em apenas 2,5% dos pacientes 180 .…”

“…Entretanto, diferentemente do trastuzumabe, a cardiotoxicidade desse fármaco é evento raro, sendo descrita redução assintomática da FEVE em apenas 2,5% dos pacientes 180 . Erlotinibe e gefitinibe: esses fármacos são iTQs anti-EGFR ativos por via oral.…”