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首页> 外文期刊>Nature clinical practice. Oncology >Drug Insight: intracellular inhibitors of HER2--clinical development of lapatinib in breast cancer.
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Drug Insight: intracellular inhibitors of HER2--clinical development of lapatinib in breast cancer.

机译:药物洞察:拉帕替尼在乳腺癌中的HER2临床开发的细胞内抑制剂。

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Targeting the human epidermal growth factor receptor type 2 (HER2) in breast cancer patients whose tumors overexpress HER2 has been clearly demonstrated to be effective in clinical trials with the monoclonal antibody trastuzumab. Not all patients, however, respond to trastuzumab therapy. Lapatinib is an oral receptor tyrosine kinase inhibitor that targets HER2 and the EGFR. Preclinical data reveal that lapatinib has activity in trastuzumab-resistant cell lines as well as synergistic activity with trastuzumab. In a pivotal phase III trial, a combination of lapatinib and capecitabine significantly decreased the risk of disease progression relative to capecitabine alone in women with HER2-positive advanced or metastatic breast cancer previously treated with anthracyclines, taxanes, and trastuzumab. Other trials are evaluating lapatinib in inflammatory breast cancer--for which encouraging data have been reported--in combination with hormone therapy, in combination with trastuzumab, and as an adjunct to adjuvant therapy for early-stage disease. Notably, lapatinib has not been associated with serious or symptomatic cardiotoxicity in clinical trials. It can cross the blood-brain barrier and might therefore have a role in preventing central-nervous-system progression. These features make lapatinib an ideal agent to evaluate more fully in HER2-positive metastatic and early-stage breast cancer.
机译:在肿瘤过度表达HER2的乳腺癌患者中,针对人类表皮生长因子受体2型(HER2)的靶向已明确证明在单克隆抗体曲妥珠单抗的临床试验中是有效的。但是,并非所有患者都对曲妥珠单抗治疗有反应。拉帕替尼是靶向HER2和EGFR的口服受体酪氨酸激酶抑制剂。临床前数据显示,拉帕替尼在曲妥珠单抗耐药细胞系中具有活性,并且与曲妥珠单抗具有协同活性。在一项关键的III期试验中,与先前使用蒽环类,紫杉烷类和曲妥珠单抗治疗的HER2阳性晚期或转移性乳腺癌女性相比,拉帕替尼和卡培他滨的组合相对于单用卡培他滨显着降低了疾病进展的风险。其他试验正在评估拉帕替尼在炎性乳腺癌中的应用(已报道了令人鼓舞的数据),结合激素疗法,曲妥珠单抗,以及作为早期疾病辅助疗法的辅助手段。值得注意的是,拉帕替尼在临床试验中并未与严重或有症状的心脏毒性相关。它可以穿越血脑屏障,因此可能在预防中枢神经系统进展中起作用。这些特征使拉帕替尼成为理想的药物,可以更全面地评估HER2阳性转移性和早期乳腺癌。

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