Awada A, Saliba W, Bozovic-Spasojevic I
Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Drugs Today (Barc). 2011 May;47(5):335-45. doi: 10.1358/dot.2011.47.5.1584110.
Receptor tyrosine-protein kinase erbB-2 (HER2)-positive breast cancer is a specific entity with an aggressive behavior. Trastuzumab, a monoclonal antibody targeting erbB-2 (HER2) deeply transformed the outcome in patients. Nevertheless, resistance to trastuzumab is still a major concern. Lapatinib ditosylate is an orally available, small molecule targeting the tyrosine activity of the HER2 receptor. Lapatinib as a single agent and in combination therapy showed interesting activity in trastuzumab-resistant advanced tumors. In addition, lapatinib use seemed suitable in recurrent locally advanced inflammatory breast cancer and brain metastases. More recently, the Neo-ALTTO (NeoAdjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) trial showed that lapatinib in combination with trastuzumab and paclitaxel significantly improved the pathological complete response in a neoadjuvant setting. Several clinical trials are still ongoing and data that may change current clinical practice are awaited with much interest.
受体酪氨酸蛋白激酶erbB-2（HER2）阳性乳腺癌是一种具有侵袭性的特殊实体。曲妥珠单抗，一种靶向erbB-2（HER2）的单克隆抗体，极大地改变了患者的治疗结果。然而，对曲妥珠单抗的耐药性仍然是一个主要问题。拉帕替尼二对甲苯磺酸盐是一种口服可用的小分子，靶向HER2受体的酪氨酸活性。拉帕替尼作为单一药物及联合治疗在曲妥珠单抗耐药的晚期肿瘤中显示出有趣的活性。此外，拉帕替尼似乎适用于复发性局部晚期炎性乳腺癌和脑转移瘤。最近，Neo-ALTTO（新辅助拉帕替尼和/或曲妥珠单抗治疗优化）试验表明，拉帕替尼联合曲妥珠单抗和紫杉醇在新辅助治疗中显著提高了病理完全缓解率。几项临床试验仍在进行中，人们非常期待可能改变当前临床实践的数据。
