Lapatinib and breast cancer: current indications and outlook for the future.
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.
Moreira
Cynthia
C
Department of Medicine, Division of Hematology/Oncology, Feinberg School of Medicine of Northwestern University and the Robert H Lurie Comprehensive Cancer Center, 676 North St Clair Street, Suite 850, Chicago, IL 60611, USA.
Kaklamani
Virginia
V
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000639:trends; D005260:Female; D005544:Forecasting; D006801:Humans; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D011799:Quinazolines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis
D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human