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.
Expert Rev Anticancer Ther. 2010 Aug;10(8):1171-82. doi: 10.1586/era.10.113.
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.
拉帕替尼是一种口服双重 erbB1/2 酪氨酸激酶抑制剂，可抑制人表皮生长因子受体 2（HER2）并阻断表皮生长因子受体。研究表明，在曲妥珠单抗耐药的转移性 HER2 阳性乳腺癌患者中，加用拉帕替尼联合卡培他滨可改善无进展生存期，并似乎延长总生存期。此外，拉帕替尼已在涉及中枢神经系统的患者中进行了研究，并与稳定疾病和一些反应相关。其与来曲唑联合使用与来曲唑单药相比，可改善激素受体阳性、HER2 阳性转移性乳腺癌患者的无进展生存期。最近的数据表明，与单药拉帕替尼相比，拉帕替尼联合曲妥珠单抗可显著改善转移性乳腺癌患者的总生存期。目前在美国，拉帕替尼的适应证为治疗转移性 HER2 阳性乳腺癌，包括与卡培他滨联合用于已接受紫杉烷、蒽环类药物和曲妥珠单抗治疗的患者，以及与来曲唑联合用于激素受体和 HER2 过表达的绝经后乳腺癌患者。拉帕替尼的常见副作用包括腹泻和皮疹。迄今为止的研究发现，其发生心脏毒性的风险小于 2%，尽管研究期间发生的大多数心脏事件都与拉帕替尼无关。重要的是要考虑到现有研究中的大多数患者已经接受了曲妥珠单抗治疗，没有明显的心脏毒性；因此，未来的研究将显示未经曲妥珠单抗治疗的患者对拉帕替尼的耐受性。正在进行的研究评估了拉帕替尼作为单一药物或与曲妥珠单抗联合用于辅助治疗的作用。
